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Daylight Saving Time: Saving light but endangering health
The American Academy of Sleep Medicine recently published its position statement reaffirming its support of utilizing permanent Standard Time (ST) as opposed to Daylight Saving Time (DST).1 DST usually occurs on the second Sunday in March when we “spring forward” by advancing the clock by 1 hour. The analogous “fall back” on the first Sunday in November refers to reversion back to the original ST, which is more synchronous with the sun’s natural pattern of rise and fall.
The earliest argument for DST practice dates back to the 1700s when Benjamin Franklin wrote a satirical piece in the Journal of Paris suggesting that advancing the clock to rise earlier in the summer would lead to economization in candle usage and save significant resources for Parisians. The modern version of this assertion infers that increased daylight in the evening will lead to increased consumer activity and work productivity with consequent economic benefits. Interestingly, the adoption of DST has demonstrated the opposite—a reduction in work productivity and economic losses.2 Another often-cited claim is that increased daylight in the evening could lead to fewer motor vehicle accidents. However, the reality is that DST is associated with more frequent car accidents in the morning.
The greatest drawback of DST is that, initially, it leads to sleep deprivation and chronically drives asynchronization between the circadian clock and the social clock. Humans synchronize their internal clock based on several factors, including light, temperature, feeding, and social habits. However, light is the strongest exogenous factor that regulates the internal clock. Light inhibits secretion of melatonin, an endogenous hormone that promotes sleep onset. While there is some individual variation in circadian patterns, exposure to bright light in the morning leads to increased physical, mental, and goal-directed activity.
Conversely, darkness or reduced light exposure in the evening hours promotes decreased activity and sleep onset via melatonin release. DST disrupts this natural process by promoting increased light exposure in the evening. This desynchronizes solar light from our internal clocks, causing a relative phase delay. Acutely, patients experience a form of imposed social jet lag. They lose an hour of sleep due to diminished sleep opportunity, as work and social obligations are typically not altered to allow for a later awakening. With recurrent delays, this lends to a pattern of chronic sleep deprivation which has significant health consequences.
Losing an hour of sleep opportunity as the clock advances in spring has dire consequences. The transition to DST is associated with increased cardiovascular events, including myocardial infarction, stroke, and admissions for acute atrial fibrillation.3 4 5 A large body of work has shown that acute reduction of sleep is associated with higher sympathetic tone, compromised immunity, and increased inflammation. Further, cognitive consequences can ensue in the form of altered situational awareness, increased risky behavior, and worse reaction time—which manifest as increased motor vehicle accidents, injuries, and fatalities.6 Emergency room visits and bounce-back admissions, medical errors and injuries, and missed appointments increase following the switch to DST.7 Psychiatric outcomes, including deaths due to suicide and overdose, are worse with the spring transition.8
Is the problem with DST merely limited to springtime, when we lose an hour of sleep? Not quite. During the “fall back” period, despite theoretically gaining an hour of sleep opportunity, people exhibit evidence of sleep disruption, psychiatric issues, traffic accidents, and inflammatory bowel disease exacerbations. These consequences likely stem from a discordance between circadian and social time, which leads to an earlier awakening based on circadian physiology as opposed to the clock time.
The acute impact of changing our sleep patterns during transitions in clock time may be appreciated more readily, but the damage is much more insidious. Chronic exposure to light in the late evening creates a state of enhanced arousal when the body should be winding down. The chronic incongruency between clock and solar time leads to dyssynchrony in our usual functions, such as food intake, social and physical activity, and basal temperature. Consequently, there is an impetus to fall asleep later. This leads to an accumulation of sleep debt and its associated negative consequences in the general, already chronically sleep-deprived population. This is especially impactful to adolescents and young adults who tend to have a delay in their sleep and wake patterns and, yet, are socially bound to early morning awakenings for school or work.
The scientific evidence behind the health risk and benefit profile of DST and ST is incontrovertible and in favor of ST. The hallmark of appropriate sleep habits involves consistency and appropriate duration. Changing timing forward or backward increases the likelihood of an alteration of the baseline established sleep and circadian consistency.
Unfortunately, despite multiple polls demonstrating the populace’s dislike of DST, repeat attempts to codify DST and negate ST persist. The latest initiative, the Sunshine Protection Act, which promised permanent DST, was passed by the US Senate but was thankfully foiled by Congress in 2022. The act of setting a time is not one that should be taken lightly or in isolation because there are significant, long-lasting health, safety, and socioeconomic consequences of this decision. Practically, this entails a concerted effort from all major economies since consistency is essential for trade and geopolitical relations. China, Japan, and India don’t practice DST. The European Parliament voted successfully to abolish DST in the European Union in 2019 with a plan to implement ST in 2021. Implementation has yet to be successful due to interruptions from the COVID-19 pandemic as well as the current economic and political climate in Europe. Political or theoretical political victories should not supersede the health and safety of an elected official’s constituents. As a medical community, we should continue to use our collective voice to encourage our representatives to vote in ways that positively affect our patients’ health outcomes.
References:
1. Rishi MA, et al. JCSM. 2024;20(1):121.
2. Gibson M, et al. Rev Econ Stat. 2018;100(5):783.
3. Jansky I, et al. N Engl J Med. 2008;359(18):1966.
4. Sipilia J, et al. Sleep Med. 2016;27-28:20.
5. Chudow JJ, et al. Sleep Med. 2020;69:155.
6. Fritz J, et al. Curr Biol. 2020;30(4):729.
7. Ferrazzi E, et al. J Biol Rhythms. 2018;33(5):555-564.
8. Berk M, et al. Sleep Biol Rhythms. 2008;6(1):22.
The American Academy of Sleep Medicine recently published its position statement reaffirming its support of utilizing permanent Standard Time (ST) as opposed to Daylight Saving Time (DST).1 DST usually occurs on the second Sunday in March when we “spring forward” by advancing the clock by 1 hour. The analogous “fall back” on the first Sunday in November refers to reversion back to the original ST, which is more synchronous with the sun’s natural pattern of rise and fall.
The earliest argument for DST practice dates back to the 1700s when Benjamin Franklin wrote a satirical piece in the Journal of Paris suggesting that advancing the clock to rise earlier in the summer would lead to economization in candle usage and save significant resources for Parisians. The modern version of this assertion infers that increased daylight in the evening will lead to increased consumer activity and work productivity with consequent economic benefits. Interestingly, the adoption of DST has demonstrated the opposite—a reduction in work productivity and economic losses.2 Another often-cited claim is that increased daylight in the evening could lead to fewer motor vehicle accidents. However, the reality is that DST is associated with more frequent car accidents in the morning.
The greatest drawback of DST is that, initially, it leads to sleep deprivation and chronically drives asynchronization between the circadian clock and the social clock. Humans synchronize their internal clock based on several factors, including light, temperature, feeding, and social habits. However, light is the strongest exogenous factor that regulates the internal clock. Light inhibits secretion of melatonin, an endogenous hormone that promotes sleep onset. While there is some individual variation in circadian patterns, exposure to bright light in the morning leads to increased physical, mental, and goal-directed activity.
Conversely, darkness or reduced light exposure in the evening hours promotes decreased activity and sleep onset via melatonin release. DST disrupts this natural process by promoting increased light exposure in the evening. This desynchronizes solar light from our internal clocks, causing a relative phase delay. Acutely, patients experience a form of imposed social jet lag. They lose an hour of sleep due to diminished sleep opportunity, as work and social obligations are typically not altered to allow for a later awakening. With recurrent delays, this lends to a pattern of chronic sleep deprivation which has significant health consequences.
Losing an hour of sleep opportunity as the clock advances in spring has dire consequences. The transition to DST is associated with increased cardiovascular events, including myocardial infarction, stroke, and admissions for acute atrial fibrillation.3 4 5 A large body of work has shown that acute reduction of sleep is associated with higher sympathetic tone, compromised immunity, and increased inflammation. Further, cognitive consequences can ensue in the form of altered situational awareness, increased risky behavior, and worse reaction time—which manifest as increased motor vehicle accidents, injuries, and fatalities.6 Emergency room visits and bounce-back admissions, medical errors and injuries, and missed appointments increase following the switch to DST.7 Psychiatric outcomes, including deaths due to suicide and overdose, are worse with the spring transition.8
Is the problem with DST merely limited to springtime, when we lose an hour of sleep? Not quite. During the “fall back” period, despite theoretically gaining an hour of sleep opportunity, people exhibit evidence of sleep disruption, psychiatric issues, traffic accidents, and inflammatory bowel disease exacerbations. These consequences likely stem from a discordance between circadian and social time, which leads to an earlier awakening based on circadian physiology as opposed to the clock time.
The acute impact of changing our sleep patterns during transitions in clock time may be appreciated more readily, but the damage is much more insidious. Chronic exposure to light in the late evening creates a state of enhanced arousal when the body should be winding down. The chronic incongruency between clock and solar time leads to dyssynchrony in our usual functions, such as food intake, social and physical activity, and basal temperature. Consequently, there is an impetus to fall asleep later. This leads to an accumulation of sleep debt and its associated negative consequences in the general, already chronically sleep-deprived population. This is especially impactful to adolescents and young adults who tend to have a delay in their sleep and wake patterns and, yet, are socially bound to early morning awakenings for school or work.
The scientific evidence behind the health risk and benefit profile of DST and ST is incontrovertible and in favor of ST. The hallmark of appropriate sleep habits involves consistency and appropriate duration. Changing timing forward or backward increases the likelihood of an alteration of the baseline established sleep and circadian consistency.
Unfortunately, despite multiple polls demonstrating the populace’s dislike of DST, repeat attempts to codify DST and negate ST persist. The latest initiative, the Sunshine Protection Act, which promised permanent DST, was passed by the US Senate but was thankfully foiled by Congress in 2022. The act of setting a time is not one that should be taken lightly or in isolation because there are significant, long-lasting health, safety, and socioeconomic consequences of this decision. Practically, this entails a concerted effort from all major economies since consistency is essential for trade and geopolitical relations. China, Japan, and India don’t practice DST. The European Parliament voted successfully to abolish DST in the European Union in 2019 with a plan to implement ST in 2021. Implementation has yet to be successful due to interruptions from the COVID-19 pandemic as well as the current economic and political climate in Europe. Political or theoretical political victories should not supersede the health and safety of an elected official’s constituents. As a medical community, we should continue to use our collective voice to encourage our representatives to vote in ways that positively affect our patients’ health outcomes.
References:
1. Rishi MA, et al. JCSM. 2024;20(1):121.
2. Gibson M, et al. Rev Econ Stat. 2018;100(5):783.
3. Jansky I, et al. N Engl J Med. 2008;359(18):1966.
4. Sipilia J, et al. Sleep Med. 2016;27-28:20.
5. Chudow JJ, et al. Sleep Med. 2020;69:155.
6. Fritz J, et al. Curr Biol. 2020;30(4):729.
7. Ferrazzi E, et al. J Biol Rhythms. 2018;33(5):555-564.
8. Berk M, et al. Sleep Biol Rhythms. 2008;6(1):22.
The American Academy of Sleep Medicine recently published its position statement reaffirming its support of utilizing permanent Standard Time (ST) as opposed to Daylight Saving Time (DST).1 DST usually occurs on the second Sunday in March when we “spring forward” by advancing the clock by 1 hour. The analogous “fall back” on the first Sunday in November refers to reversion back to the original ST, which is more synchronous with the sun’s natural pattern of rise and fall.
The earliest argument for DST practice dates back to the 1700s when Benjamin Franklin wrote a satirical piece in the Journal of Paris suggesting that advancing the clock to rise earlier in the summer would lead to economization in candle usage and save significant resources for Parisians. The modern version of this assertion infers that increased daylight in the evening will lead to increased consumer activity and work productivity with consequent economic benefits. Interestingly, the adoption of DST has demonstrated the opposite—a reduction in work productivity and economic losses.2 Another often-cited claim is that increased daylight in the evening could lead to fewer motor vehicle accidents. However, the reality is that DST is associated with more frequent car accidents in the morning.
The greatest drawback of DST is that, initially, it leads to sleep deprivation and chronically drives asynchronization between the circadian clock and the social clock. Humans synchronize their internal clock based on several factors, including light, temperature, feeding, and social habits. However, light is the strongest exogenous factor that regulates the internal clock. Light inhibits secretion of melatonin, an endogenous hormone that promotes sleep onset. While there is some individual variation in circadian patterns, exposure to bright light in the morning leads to increased physical, mental, and goal-directed activity.
Conversely, darkness or reduced light exposure in the evening hours promotes decreased activity and sleep onset via melatonin release. DST disrupts this natural process by promoting increased light exposure in the evening. This desynchronizes solar light from our internal clocks, causing a relative phase delay. Acutely, patients experience a form of imposed social jet lag. They lose an hour of sleep due to diminished sleep opportunity, as work and social obligations are typically not altered to allow for a later awakening. With recurrent delays, this lends to a pattern of chronic sleep deprivation which has significant health consequences.
Losing an hour of sleep opportunity as the clock advances in spring has dire consequences. The transition to DST is associated with increased cardiovascular events, including myocardial infarction, stroke, and admissions for acute atrial fibrillation.3 4 5 A large body of work has shown that acute reduction of sleep is associated with higher sympathetic tone, compromised immunity, and increased inflammation. Further, cognitive consequences can ensue in the form of altered situational awareness, increased risky behavior, and worse reaction time—which manifest as increased motor vehicle accidents, injuries, and fatalities.6 Emergency room visits and bounce-back admissions, medical errors and injuries, and missed appointments increase following the switch to DST.7 Psychiatric outcomes, including deaths due to suicide and overdose, are worse with the spring transition.8
Is the problem with DST merely limited to springtime, when we lose an hour of sleep? Not quite. During the “fall back” period, despite theoretically gaining an hour of sleep opportunity, people exhibit evidence of sleep disruption, psychiatric issues, traffic accidents, and inflammatory bowel disease exacerbations. These consequences likely stem from a discordance between circadian and social time, which leads to an earlier awakening based on circadian physiology as opposed to the clock time.
The acute impact of changing our sleep patterns during transitions in clock time may be appreciated more readily, but the damage is much more insidious. Chronic exposure to light in the late evening creates a state of enhanced arousal when the body should be winding down. The chronic incongruency between clock and solar time leads to dyssynchrony in our usual functions, such as food intake, social and physical activity, and basal temperature. Consequently, there is an impetus to fall asleep later. This leads to an accumulation of sleep debt and its associated negative consequences in the general, already chronically sleep-deprived population. This is especially impactful to adolescents and young adults who tend to have a delay in their sleep and wake patterns and, yet, are socially bound to early morning awakenings for school or work.
The scientific evidence behind the health risk and benefit profile of DST and ST is incontrovertible and in favor of ST. The hallmark of appropriate sleep habits involves consistency and appropriate duration. Changing timing forward or backward increases the likelihood of an alteration of the baseline established sleep and circadian consistency.
Unfortunately, despite multiple polls demonstrating the populace’s dislike of DST, repeat attempts to codify DST and negate ST persist. The latest initiative, the Sunshine Protection Act, which promised permanent DST, was passed by the US Senate but was thankfully foiled by Congress in 2022. The act of setting a time is not one that should be taken lightly or in isolation because there are significant, long-lasting health, safety, and socioeconomic consequences of this decision. Practically, this entails a concerted effort from all major economies since consistency is essential for trade and geopolitical relations. China, Japan, and India don’t practice DST. The European Parliament voted successfully to abolish DST in the European Union in 2019 with a plan to implement ST in 2021. Implementation has yet to be successful due to interruptions from the COVID-19 pandemic as well as the current economic and political climate in Europe. Political or theoretical political victories should not supersede the health and safety of an elected official’s constituents. As a medical community, we should continue to use our collective voice to encourage our representatives to vote in ways that positively affect our patients’ health outcomes.
References:
1. Rishi MA, et al. JCSM. 2024;20(1):121.
2. Gibson M, et al. Rev Econ Stat. 2018;100(5):783.
3. Jansky I, et al. N Engl J Med. 2008;359(18):1966.
4. Sipilia J, et al. Sleep Med. 2016;27-28:20.
5. Chudow JJ, et al. Sleep Med. 2020;69:155.
6. Fritz J, et al. Curr Biol. 2020;30(4):729.
7. Ferrazzi E, et al. J Biol Rhythms. 2018;33(5):555-564.
8. Berk M, et al. Sleep Biol Rhythms. 2008;6(1):22.
Patients haunted by fears of living with and dying from severe lung disease
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Many patients with chronic progressive pulmonary disease feel anxious and depressed as their conditions advance, as breathing becomes increasingly labored and difficult, and as performing even small daily tasks leaves them exhausted.
Persons with severe COPD frequently report fears of suffocation and death, as well as anxieties about abandoning family and friends, and these negative, intrusive thoughts can have an adverse effect on COPD outcomes.
Disease-related mental distress can lead to increased disability, more frequent use of costly health care resources, higher morbidity, and elevated risk of death, investigators say.
"Individuals with severe COPD are twice as likely to develop depression than patients with mild COPD. Prevalence rates for clinical anxiety in COPD range from 13% to 46% in outpatients and 10% to 55% among inpatients," wrote Abebaw Mengitsu Yohannes, PhD, then from Azusa Pacific University in Azusa, California and colleagues in an article published jointly by The Journal of Family Practice and The Cleveland Clinic Journal of Medicine.
Patients with COPD may experience major depressive disorders, chronic mild depression (dysthymias), and minor depression, as well as generalized anxiety disorder, phobias, and panic disorders, the investigators say.
"Growing evidence suggests that the relationship between mood disorders, particularly depression, and COPD is bidirectional, meaning that mood disorders adversely impact prognosis in COPD, whereas COPD increases the risk of developing depression," Yohannes et al wrote.
Jamie Garfield, MD, professor of thoracic medicine and surgery at Temple University's Lewis Katz School of Medicine in Philadelphia, told Chest Physician that the association between severe chronic diseases and mood disorders is well known.
"I don't think that it's specific to chronic lung diseases; in people with chronic heart disease or malignancies we see that co-existence of depression and anxiety will worsen the course of disease," she said.
Dr. Johannes, who is currently a professor of physical therapy at the University of Alabama School of Health Professionals in Birmingham, said that depression and anxiety are often underdiagnosed and undertreated in patients with obstructive pulmonary diseases because the conditions can share symptoms such as dyspnea (for example, in anxiety) or fatigue (in depression).
"Therefore, unless one begins to explore further, it's hard for physicians to be able to identify these conditions," he said in an interview with Chest Physician.
Fears of dying (and living)
The causes of depression and anxiety among patients with obstructive pulmonary disorders are multi-factorial, and may require a variety of treatment and coping strategies, according to Susann Strang, RN, PhD, and colleagues from the University of Gothenburg, Sweden.
They conducted qualitative in-depth interviews with 31 men and women with stage III or IV COPD, and found that the majority of patients had anxiety associated with their disease.
"Analyses revealed three major themes: death anxiety, life anxiety, and counterweights to anxiety," the investigators wrote in a study published in the journal Palliative and Supportive Care in 2014.
Factors contributing to anxiety surrounding death included fear of suffocation, awareness of impending death, fear of the process of death, and anxiety about being separated from loved ones.
In contrast, some patients expressed dread of living with the limitations and loneliness imposed on them by their disease, so called "life anxiety."
The patients also reported "counterweights" to anxiety as a way of coping. For some this involved trust in their health care professionals and adherence to medication, inhalers, and supplemental oxygen.
"The patients also placed hope in new treatments, better medication, surgery, stem cell treatment, or lung transplants," Dr. Strang and colleagues reported.
Others reported avoiding talking about death, sleeping more, or using humor to "laugh off this difficult subject."
Screening and diagnosis
Primary care practitioners are often the first health professionals that patients with COPD see, but these clinicians often don't have the time to add screening to their already crammed schedules. In addition, "the lack of a standardized approach in diagnosis, and inadequate knowledge or confidence in assessing psychological status (particularly given the number of strategies available for screening patients for mood disorders)," can make it difficult for PCPs to detect and manage anxiety and depression in their patients with significant health care burdens from COPD and other obstructive lung diseases, Dr. Yohannes and colleagues noted.
In addition to commonly used screening tools for anxiety and depression such as the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire (PHQ-9), there are at least two designed to evaluate patients with lung disease: the Anxiety Inventory for Respiratory (AIR) Disease scale, developed by Dr. Johannes and colleagues, and the COPD Anxiety Questionnaire.
The COPD Assessment Testand Clinical COPD Questionnaire, while not specifically designed to screen for mental disorders, include questions that can point to symptoms of distress in patients with COPD, Dr. Yohannes said.
"In truth I think that there are few providers who will routinely do this on all their patients in terms of quantifying the severity or the presence or absence of depression, but in my own practice I very much ask questions that align with the questions in these tools to determine whether my patient appears to have high levels of anxiety and depression," Dr. Garfield said.
Listen to patients and families
Among the most powerful tools that clinicians have at their disposal for treating anxiety and depression in patients with chronic lung disease are their ears and their minds, said Anthony Saleh, MD, a pulmonologist at New York-Presbyterian Brooklyn Methodist Hospital in Brooklyn, New York.
"I think just listening to the patient, that's a little bit forgotten yet so important," he said in an interview with Chest Physician.
"When I have someone with advanced lung disease, like idiopathic pulmonary fibrosis, like advanced emphysema, one of the most important things I think is to listen to the patient, and not just to listen to the answers of your perfunctory 'how's your breathing? Any chest pain?' and those sort of rote medical questions, but listen to their thoughts, and it will given them a safe space to say 'Hey, I'm nervous, hey I'm worried about my family, hey I'm worried if I die what's going to happen to my wife and kids,' and that's something I think is invaluable."
It's also vital to listen to the concerns of the patients family members, who may be the primary caregivers and may share the patient's stresses and anxieties, he said.
Pulmonary Rehabilitation
All of the experts interviewed for this article agreed that a combination of medical, social and mental health support services is important for treatment for patients with chronic obstructive lung diseases.
One of the most effective means of helping patients with both acute breathing problems and with disease-related anxiety and depression is pulmonary rehabilitation. Depending on disease severity, this multidisciplinary approach may involve exercise, patient education, psychological and nutrition counseling, and training patients how to conserve energy and adopt breathing strategies to help them better manage their symptoms.
"I think that pulmonary rehabilitation is one of the first interventions that we should be recommending for our patients," Dr. Garfield said. "It's physical therapy for patients with chronic lung diseases, backed by respiratory therapists, and it offers not only physical rehabilitation - improving strength and coordination, but also it helps our patients get as much as possible out of what they've got."
For example, patients can be taught how to decrease their respiratory rate when they're feeling a sense of urgency or panic. Patients can also learn how to change body positions to help them breathe more effectively when they feel that their breath is limited or restricted, she said.
"Once your into medical interventions, pulmonary rehab is phenomenal," Dr. Saleh said.
Pulmonary rehabilitation helps patients to feel better about themselves and about their abilities, but "unfortunately it's not as available as we like," he said.
Many patients don't live near a pulmonary rehabilitation center, and the typical two to three weekly sessions for 4 to 12 weeks or longer can be a significant burden for patients and caregivers, he acknowledged.
"You have to sit [with the patient] and be honest and tell them it's a lot of diligence involved and you have to be really motivated," he said.
Other treatment options include pharmacological therapy with antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and anxiolytic agents.
"SSRIs are the current first-line drug treatment for depression, and have been shown to significantly improve depression and anxiety in patients with COPD in some, but not all, trials published to date. However, it is important to note that a diagnosis of bipolar disorder must be ruled out before initiating standard antidepressant therapy," Dr. Johannes and colleagues wrote.
Defiant joy
Importantly, even with the burden of life with COPD, many patients found ways to experience what Strang et al called "a defiant joy."
"It was remarkable that when the patients were asked about what gave their lives meaning today, many talked about what had given their life meaning in the past, prior to becoming ill. In the light of the things they had lost because of the disease, many felt that their previous sources of joy no longer existed. Despite this, many still hoped to be able to get out into the fresh air, to be able to do errands or that tomorrow might be better," the investigators wrote.
Dr. Yohannes, Dr. Garfield, and Dr. Saleh all reported having no relevant conflicts of interest to report.
Older Age Confers a Higher Risk for Second Primary Melanoma: Study
TOPLINE:
.
METHODOLOGY:
- Knowledge about one’s risk for a second primary invasive melanoma over time remains incomplete.
- Using data from the Cancer Registry of Norway, researchers performed a cohort study of 19,196 individuals diagnosed with invasive melanomas during 2008-2020; 51% were women. The mean age at the first primary melanoma diagnosis was 62 years.
- The main outcome of interest was the incidence rate of second primary invasive melanoma after the first diagnosis.
- The researchers used accelerated failure time models to examine potential associations with patient and tumor characteristics. They also calculated the median time between first and second melanomas and the likelihood of second primary melanomas on the same or different site as the first primary melanoma.
TAKEAWAY:
- The incidence rate of a second primary melanoma in the year following a first primary melanoma was 16.8 (95% CI, 14.9-18.7) per 1000 person-years. This decreased to 7.3 (95% CI, 6.0-8.6) per 1000 person-years during the second year and remained stable after that.
- Patient age influenced the median time between first and second primaries. The median interval was 37 months (95% CI, 8-49) in patients aged < 40 years, 18 months (95% CI, 13-24) in patients aged 50-59 years, and 11 months (95% CI, 7-18) in patients aged ≥ 80 years.
- The body site of the second primary melanoma was the same as the first primary in 47% of patients but was located on a different body site in the remaining 53% of patients.
- Among patients who developed a second primary melanoma on the same site as the first, the median interval was shorter for men compared with women: A median of 12 (95% CI, 7-19) months vs 22 (95% CI, 11-35) months, respectively.
IN PRACTICE:
“Our findings suggest that increased surveillance may be considered for older patients, especially men, for at least the first 3 years after their initial diagnosis, regardless of the characteristics of their first melanoma,” the authors wrote.
SOURCE:
Corresponding author Reza Ghiasvand, PhD, of the Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway, and colleagues conducted the research, published online on February 28, 2024, in JAMA Dermatology.
LIMITATIONS:
Information was lacking on phenotypic characteristics, personal ultraviolet radiation (UVR) exposure, genetic factors, and the number of follow-up skin examinations.
DISCLOSURES:
The study was supported by the South-Eastern Norway Regional Health Authority. The authors reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- Knowledge about one’s risk for a second primary invasive melanoma over time remains incomplete.
- Using data from the Cancer Registry of Norway, researchers performed a cohort study of 19,196 individuals diagnosed with invasive melanomas during 2008-2020; 51% were women. The mean age at the first primary melanoma diagnosis was 62 years.
- The main outcome of interest was the incidence rate of second primary invasive melanoma after the first diagnosis.
- The researchers used accelerated failure time models to examine potential associations with patient and tumor characteristics. They also calculated the median time between first and second melanomas and the likelihood of second primary melanomas on the same or different site as the first primary melanoma.
TAKEAWAY:
- The incidence rate of a second primary melanoma in the year following a first primary melanoma was 16.8 (95% CI, 14.9-18.7) per 1000 person-years. This decreased to 7.3 (95% CI, 6.0-8.6) per 1000 person-years during the second year and remained stable after that.
- Patient age influenced the median time between first and second primaries. The median interval was 37 months (95% CI, 8-49) in patients aged < 40 years, 18 months (95% CI, 13-24) in patients aged 50-59 years, and 11 months (95% CI, 7-18) in patients aged ≥ 80 years.
- The body site of the second primary melanoma was the same as the first primary in 47% of patients but was located on a different body site in the remaining 53% of patients.
- Among patients who developed a second primary melanoma on the same site as the first, the median interval was shorter for men compared with women: A median of 12 (95% CI, 7-19) months vs 22 (95% CI, 11-35) months, respectively.
IN PRACTICE:
“Our findings suggest that increased surveillance may be considered for older patients, especially men, for at least the first 3 years after their initial diagnosis, regardless of the characteristics of their first melanoma,” the authors wrote.
SOURCE:
Corresponding author Reza Ghiasvand, PhD, of the Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway, and colleagues conducted the research, published online on February 28, 2024, in JAMA Dermatology.
LIMITATIONS:
Information was lacking on phenotypic characteristics, personal ultraviolet radiation (UVR) exposure, genetic factors, and the number of follow-up skin examinations.
DISCLOSURES:
The study was supported by the South-Eastern Norway Regional Health Authority. The authors reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- Knowledge about one’s risk for a second primary invasive melanoma over time remains incomplete.
- Using data from the Cancer Registry of Norway, researchers performed a cohort study of 19,196 individuals diagnosed with invasive melanomas during 2008-2020; 51% were women. The mean age at the first primary melanoma diagnosis was 62 years.
- The main outcome of interest was the incidence rate of second primary invasive melanoma after the first diagnosis.
- The researchers used accelerated failure time models to examine potential associations with patient and tumor characteristics. They also calculated the median time between first and second melanomas and the likelihood of second primary melanomas on the same or different site as the first primary melanoma.
TAKEAWAY:
- The incidence rate of a second primary melanoma in the year following a first primary melanoma was 16.8 (95% CI, 14.9-18.7) per 1000 person-years. This decreased to 7.3 (95% CI, 6.0-8.6) per 1000 person-years during the second year and remained stable after that.
- Patient age influenced the median time between first and second primaries. The median interval was 37 months (95% CI, 8-49) in patients aged < 40 years, 18 months (95% CI, 13-24) in patients aged 50-59 years, and 11 months (95% CI, 7-18) in patients aged ≥ 80 years.
- The body site of the second primary melanoma was the same as the first primary in 47% of patients but was located on a different body site in the remaining 53% of patients.
- Among patients who developed a second primary melanoma on the same site as the first, the median interval was shorter for men compared with women: A median of 12 (95% CI, 7-19) months vs 22 (95% CI, 11-35) months, respectively.
IN PRACTICE:
“Our findings suggest that increased surveillance may be considered for older patients, especially men, for at least the first 3 years after their initial diagnosis, regardless of the characteristics of their first melanoma,” the authors wrote.
SOURCE:
Corresponding author Reza Ghiasvand, PhD, of the Oslo Centre for Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway, and colleagues conducted the research, published online on February 28, 2024, in JAMA Dermatology.
LIMITATIONS:
Information was lacking on phenotypic characteristics, personal ultraviolet radiation (UVR) exposure, genetic factors, and the number of follow-up skin examinations.
DISCLOSURES:
The study was supported by the South-Eastern Norway Regional Health Authority. The authors reported having no disclosures.
A version of this article appeared on Medscape.com.
Study Evaluates Factors Driving Fatigue in Patients With Psoriasis, PsA
TOPLINE:
Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.
METHODOLOGY:
- The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
- Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
- All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
- All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.
TAKEAWAY:
- Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
- Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
- Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
- In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).
IN PRACTICE:
“The when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.
SOURCE:
Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.
DISCLOSURES:
Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.
METHODOLOGY:
- The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
- Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
- All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
- All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.
TAKEAWAY:
- Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
- Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
- Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
- In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).
IN PRACTICE:
“The when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.
SOURCE:
Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.
DISCLOSURES:
Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.
A version of this article appeared on Medscape.com.
TOPLINE:
Many factors may influence fatigue in patients with psoriasis and psoriatic arthritis (PsA), researchers report.
METHODOLOGY:
- The individual components of fatigue in psoriasis and PsA have not been examined thoroughly.
- Researchers drew from the nationwide prospective Danish Skin Cohort to identify 2741 adults with dermatologist-diagnosed psoriasis (of which 593 also had PsA) and 3788 controls in the general population.
- All adults in the analysis completed the multidimensional fatigue inventory (MIF-20), a validated 20-item tool that measures five dimensions of fatigue: General fatigue, physical fatigue, reduced activity, reduced motivation, and mental fatigue. A higher score indicates more severe fatigue.
- All adults were also asked about their current intensity of joint pain over the previous 7 days, severity of pruritus and skin pain over the previous 24 hours, and sleep problems over the previous 72 hours on a numerical rating scale (NRS). The researchers applied linear regression models to continuous outcomes and adjusted for age, sex, socioeconomic status, psoriasis severity, and joint pain intensity, and beta coefficients (β) for the slopes were estimated with 95% CIs.
TAKEAWAY:
- Compared with the general population, higher total MFI-20 scores were observed for psoriasis and PsA, respectively. However, on the adjusted analysis, the impact on total fatigue was greatest for those with PsA (β = 5.23; 95% CI, 3.55-6.90), followed by psoriasis (β = 2.10; 95% CI, 0.96-3.25) compared with the general population (P trend < .0001).
- Increasing age was associated with a lower impact on total fatigue in psoriasis (β = −0.13; 95% CI, −0.18 to −0.08) and in PsA (β = −0.10; 95% CI, −0.19 to −0.01).
- Among patients with psoriasis with or without PsA, increasing joint pain intensity was associated with overall fatigue (β = 2.23; 95% CI, 2.03-2.44) for each one-point increase in joint pain on the NRS.
- In other findings, greater intensity of itch was associated with higher fatigue scores for both psoriasis and PsA, while skin pain was significantly associated with fatigue in PsA (β = 0.65; 95% CI, 0.08-1.22) but not in psoriasis without PsA (P = .2043).
IN PRACTICE:
“The when treating psoriasis, rather than focusing on objective severity measures alone,” the authors wrote.
SOURCE:
Corresponding author Alexander Egeberg, MD, of the Department of Dermatology at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark, and colleagues conducted the research, which was published in the Journal of the American Academy of Dermatology.
LIMITATIONS:
The researchers were unable to assess whether the pain was inflammatory or noninflammatory or the number of affected joints. They also lacked information about the use of methotrexate, which commonly causes fatigue.
DISCLOSURES:
Dr. Egeberg is now an employee at LEO Pharma. He has received research funding from Pfizer, Eli Lilly, the Danish National Psoriasis Foundation, and the Royal Hofbundtmager Aage Bang Foundation, and honoraria as a consultant and/or speaker from AbbVie, Almirall, Bristol-Myers Squibb, Leo Pharma, Samsung Bioepis Co., Ltd., Pfizer, Eli Lilly, Novartis, UCB, Union Therapeutics, Horizon Therapeutics, Galderma, and Janssen Pharmaceuticals. Three of the coauthors reported being a consultant to, an adviser for, and/or having received research support from many pharmaceutical companies.
A version of this article appeared on Medscape.com.
Be Wary of TikTok Content on Infantile Hemangiomas: Study
TOPLINE:
.
METHODOLOGY:
- New parents may turn to TikTok for information about IHs, but little is known about the quality of videos on the social media platform related to the topic.
- Using the search term “hemangioma,” researchers reviewed the top 50 English-language TikTok videos that resulted from the query in November 2022.
- The researchers analyzed the videos for their content source, accuracy, and purpose and used Infantile Hemangioma Referral Score criteria to determine if the lesions pictured on the videos met criteria for referral to a specialist or not.
TAKEAWAY:
- Combined, the 50 videos were viewed 25.1 million times, had 2.6 million likes, and received 17,600 comments.
- Only 36 were considered likely to be IH. Of those 36 videos, the researchers deemed 33 (92%) to be potentially problematic, meriting referral to a specialist. The remaining three lesions could not be classified because of insufficient information.
- Of the 50 videos, 45 were created by individuals personally affected by IH (parents of a child with IH or young adults living with residual impacts), and only three were created by physicians (two by plastic surgeons and one by a neonatologist).
- In terms of content, 2 of the 45 videos created by someone personally affected by IH contained inaccurate information, while all three of videos created by physicians contained inaccurate information, such as oversimplification of the prognosis or incorrect nomenclature.
IN PRACTICE:
“Providers should be aware that TikTok may be useful for promoting birthmark awareness, but that it should not be relied on for accurate information about IHs,” the authors wrote.
SOURCE:
First author Sonora Yun, a medical student at Columbia University College of Physicians and Surgeons, New York City, conducted the research with Maria C. Garzon, MD, and Kimberly D. Morel, MD, who are board-certified pediatric dermatologists at Columbia. The study was published in Pediatric Dermatology.
LIMITATIONS:
The authors noted no specific limitations to the study.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- New parents may turn to TikTok for information about IHs, but little is known about the quality of videos on the social media platform related to the topic.
- Using the search term “hemangioma,” researchers reviewed the top 50 English-language TikTok videos that resulted from the query in November 2022.
- The researchers analyzed the videos for their content source, accuracy, and purpose and used Infantile Hemangioma Referral Score criteria to determine if the lesions pictured on the videos met criteria for referral to a specialist or not.
TAKEAWAY:
- Combined, the 50 videos were viewed 25.1 million times, had 2.6 million likes, and received 17,600 comments.
- Only 36 were considered likely to be IH. Of those 36 videos, the researchers deemed 33 (92%) to be potentially problematic, meriting referral to a specialist. The remaining three lesions could not be classified because of insufficient information.
- Of the 50 videos, 45 were created by individuals personally affected by IH (parents of a child with IH or young adults living with residual impacts), and only three were created by physicians (two by plastic surgeons and one by a neonatologist).
- In terms of content, 2 of the 45 videos created by someone personally affected by IH contained inaccurate information, while all three of videos created by physicians contained inaccurate information, such as oversimplification of the prognosis or incorrect nomenclature.
IN PRACTICE:
“Providers should be aware that TikTok may be useful for promoting birthmark awareness, but that it should not be relied on for accurate information about IHs,” the authors wrote.
SOURCE:
First author Sonora Yun, a medical student at Columbia University College of Physicians and Surgeons, New York City, conducted the research with Maria C. Garzon, MD, and Kimberly D. Morel, MD, who are board-certified pediatric dermatologists at Columbia. The study was published in Pediatric Dermatology.
LIMITATIONS:
The authors noted no specific limitations to the study.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
.
METHODOLOGY:
- New parents may turn to TikTok for information about IHs, but little is known about the quality of videos on the social media platform related to the topic.
- Using the search term “hemangioma,” researchers reviewed the top 50 English-language TikTok videos that resulted from the query in November 2022.
- The researchers analyzed the videos for their content source, accuracy, and purpose and used Infantile Hemangioma Referral Score criteria to determine if the lesions pictured on the videos met criteria for referral to a specialist or not.
TAKEAWAY:
- Combined, the 50 videos were viewed 25.1 million times, had 2.6 million likes, and received 17,600 comments.
- Only 36 were considered likely to be IH. Of those 36 videos, the researchers deemed 33 (92%) to be potentially problematic, meriting referral to a specialist. The remaining three lesions could not be classified because of insufficient information.
- Of the 50 videos, 45 were created by individuals personally affected by IH (parents of a child with IH or young adults living with residual impacts), and only three were created by physicians (two by plastic surgeons and one by a neonatologist).
- In terms of content, 2 of the 45 videos created by someone personally affected by IH contained inaccurate information, while all three of videos created by physicians contained inaccurate information, such as oversimplification of the prognosis or incorrect nomenclature.
IN PRACTICE:
“Providers should be aware that TikTok may be useful for promoting birthmark awareness, but that it should not be relied on for accurate information about IHs,” the authors wrote.
SOURCE:
First author Sonora Yun, a medical student at Columbia University College of Physicians and Surgeons, New York City, conducted the research with Maria C. Garzon, MD, and Kimberly D. Morel, MD, who are board-certified pediatric dermatologists at Columbia. The study was published in Pediatric Dermatology.
LIMITATIONS:
The authors noted no specific limitations to the study.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
‘Remarkable’ Study Tracks Timeline of Biomarker Changes 20 Years Before Alzheimer’s disease
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
, something that hasn’t previously been extensively investigated in longitudinal studies.
By analyzing cerebral spinal fluid (CSF), as well as cognitive and brain imaging assessments conducted every few years for two decades, researchers were able to plot the course of changing levels of amyloid-beta 42 (Abeta42), phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) in adults with Alzheimer’s disease and mark when those levels began to deviate from those of adults without Alzheimer’s disease.
Levels of Abeta42 in CSF and the ratio of Abeta42 to Abeta40 in people who developed Alzheimer’s disease diverged from those of peers who remained cognitively normal at 18 years and 14 years, respectively, before clinical signs of disease appeared.
The level of p-tau181 in CSF increased 11 years before disease onset, and NfL levels, a measure of neurodegeneration, increased 9 years before diagnosis.
These changes were followed by hippocampal atrophy and cognitive decline a few years later.
The results also show “an apparent accelerated change in concentrations of CSF biomarkers followed by a slowing of this change up to the time of diagnosis,” report the authors, led by Jianping Jia, MD, PhD, with the Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.
The study was published online in The New England Journal of Medicine.
Time Course of Biomarker Changes
Dr. Jia and colleagues conducted a nested case-control study within the China Cognition and Aging Study (COAST). They matched 648 adults who developed Alzheimer’s disease to 648 who remained cognitively normal. CSF, cognitive, and brain imaging assessments were performed every 2-3 years for a median of about 20 years.
Within both groups, men slightly outnumbered women. At baseline, CSF biomarker levels, cognitive scores, and hippocampal volumes were similar in the two groups. Adults who developed Alzheimer’s disease were more likely than their matched controls to be carriers of the APOE epsilon-4 allele (37% vs 20%).
In terms of CSF Abeta42, the level of this biomarker in those who developed Alzheimer’s disease diverged from the level in controls an estimated 18 years before clinical diagnosis. At that time, the level was lower by a mean 59.13 pg/mL in the Alzheimer’s disease group.
A difference in the ratio of CSF Abeta42 to Abeta40 between the two groups appeared an estimated 14 years before the diagnosis of Alzheimer’s disease (difference in mean values, −0.01 pg/mL).
Differences between the two groups in CSF p-tau181 and total tau concentrations were apparent roughly 11 and 10 years before diagnosis, respectively. At those times, the mean differences in p-tau181 and total tau concentrations were 7.10 pg/mL and 87.10 pg/mL, respectively.
In terms of NfL, a difference between the groups was observed 9 years before diagnosis, with its trajectory progressively deviating from the concentrations observed in cognitively normal groups at that time, to a final mean difference in NfL of 228.29 pg/mL.
Bilateral hippocampal volume decreased with age in both groups. However, the decrease began to differ between the two groups 8 years before Alzheimer’s disease diagnosis, at which time volume was lower by 358.94 mm3 in the Alzheimer’s disease group compared with the control group.
Average Clinical Dementia Rating–Sum of Boxes (CDR-SB) scores in the Alzheimer’s disease group began to worsen compared with the control group at about 6 years before diagnosis.
As Alzheimer’s disease progressed, changes in CSF biomarkers increased before reaching a plateau.
Important Contribution
In a linked editorial, Richard Mayeux, MD, Department of Neurology, Columbia University, New York, said the importance of this work “cannot be overstated. Knowledge of the timing of these physiological events is critical to provide clinicians with useful starting points for prevention and therapeutic strategies.”
Dr. Mayeux said this “remarkable” longitudinal study spanning 2 decades “not only confirms the hypotheses of previous investigators but extends and validates the sequence of changes” in sporadic Alzheimer’s disease.
Dr. Mayeux acknowledged that one might consider the finding in this study to be limited owing to the inclusion of only individuals of Han Chinese ancestry.
However, longitudinal studies of plasma biomarkers in individuals of Asian, European, African, and Hispanic ancestry have shown similar trends in biomarker changes preceding the onset of Alzheimer’s disease, he noted.
“Ethnic variation in these biomarkers is known, but that fact does not lessen the effect of the results reported. It merely highlights that similar studies must continue and must be inclusive of other groups,” Dr. Mayeux concluded.
The study had no commercial funding. Disclosures for authors and editorialist are available at NEJM.org.
A version of this article appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Omalizumab for Food Allergies: What PCPs Should Know
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Sandra Hong, MD, chair of allergy and immunology and director of the Food Allergy Center of Excellence at Cleveland Clinic, in Ohio, sees firsthand how situations that feel ordinary to most people strike fear in the hearts of her patients with food allergies.
Not only do some experience reactions to milk when they eat a cheese pizza — they can’t be in the same room with someone enjoying a slice nearby. “That would be terrifying,” Dr. Hong said.
Omalizumab (Xolair), recently approved by the US Food and Drug Administration as monotherapy for the treatment of food allergies, may now bring peace of mind to these patients and their families by reducing their risk of dangerous allergic reactions to accidental exposure.
While the drug does not cure food allergies, a phase 3, placebo-controlled trial found that after 16 weeks of treatment, two thirds of participants were able to tolerate at least 600 mg of peanut protein — equal to about 2.5 peanuts — without experiencing moderate to severe reactions.
An open-label extension trial also found the monoclonal antibody reduced the likelihood of serious reactions to eggs by 67%, milk by 66%, and cashews by 42%. The results of the study were published in The New England Journal of Medicine.
The treatment is approved for children as young as the age of 1 year and is the only treatment approved for multiple food allergies. It does not treat anaphylaxis or other emergency situations.
Patient Selection Key
While 8% of children and 10% of adults in the United States have a true food allergy, Brian Vickery, MD, chief of allergy and immunology and director of the Food Allergy Center at Children’s Healthcare of Atlanta, noted that a significantly higher proportion of the population restricts their diet based on perceived food intolerances.
“Most important for family doctors prior to prescribing the medication will be to be sure that the diagnosis is correct,” Kim said. “We know that allergy blood and skin testing is good but not perfect, and false positive results can occur,” said Edwin Kim, MD, chief of the Division of Pediatric Allergy and Immunology and director of the University of North Carolina Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill, who was a coauthor on the study in the New England Journal of Medicine. “ An allergist can conduct food challenges to confirm the diagnosis if results are unclear.”
Even for patients with confirmed IgE-mediated allergies, Dr. Hong said selecting patients who are good candidates for the therapy has “nuances.”
Patients must be willing and able to commit to injections every 2-4 weeks. Dosing depends on body weight and the total IgE levels of each patient. Patients with IgE levels > 1850 UI/mL likely will be disqualified from treatment since the clinical trial did not enroll patients with total IgE above this level and the appropriate dose in those patients is unknown.
“My recommendation for family physicians who are counseling food-allergic patients interested in omalizumab treatment is to partner with an allergist-immunologist, if at all possible,” Dr. Vickery said. He added that patients should have a comprehensive workup before beginning treatment because starting omalizumab would reduce reactivity and alter the outcome a diagnostic oral food challenge.
Two populations Dr. Hong thinks might particularly benefit from the therapy are college students and preschoolers, who may be unable to completely avoid allergens because of poor impulse control and food sharing in group settings.
“The concerns we have about this age group are whether or not there might be other factors involved that may impede their ability to make good decisions.”
Less control of the environment in dorms or other group living situations also could increase the risk of accidental exposure to a food allergen.
For the right patients, the treatment regimen has significant advantages over oral immunotherapy treatment (OIT), including the fact that it’s not a daily medication and it has the potential to treat allergic asthma at the same time.
“The biggest pro for omalizumab is that it can treat all of your food allergies, whether you have one or many, and do it all in one medication,” Dr. Kim said.
Managing Potential Harms
Omalizumab carries risks both primary care providers and patients must consider. First among them is that the drug carries a “black box” warning for an increased risk of anaphylaxis, Dr. Hong said.
Although patients with multiple food allergies typically already have prescriptions for epinephrine, primary care physicians (PCPs) considering offering omalizumab must be comfortable treating severe systemic reactions and their offices capable of post-dose monitoring, Dr. Hong said.
Anaphylaxis “can occur after the first dose or it can be delayed,” she said. “Typically, allergists will give these in our offices and we’ll actually have people wait for delayed amounts of time, for hours.”
The drug has been available since 2003 as a treatment for allergic asthma and urticaria. In addition to the warning for anaphylaxis, common reactions include joint pain and injection-site reactions. It also increases the risk for parasitic infection, and some studies show an increase in the risk for cancer.
Still, Dr. Kim said omalizumab’s safety profile is reassuring and noted it has advantages over OIT. “Since the patient is not exposing themselves to the food they are allergic to like in OIT, the safety is expected to be far better,” he said.
Lifelong Treatment
Dr. Vickery, Dr. Hong, and Dr. Kim all cautioned that patients should understand that, while omalizumab offers protection against accidental exposure and can meaningfully improve quality of life, it won’t allow them to loosen their allergen-avoidant diets.
Further, maintaining protection requires receiving injections every 2-4 weeks for life. For those without insurance, or whose insurance does not cover the treatment, costs could reach thousands of dollars each month, Dr. Hong said.
Omalizumab “has been well covered by insurance for asthma and chronic hives, but we will have to see what it looks like for food allergy. The range of plans and out-of-pocket deductibles available to patients will also play a big role,” Dr. Kim said.
Other novel approaches to food allergies are currently in clinical trials, and both Dr. Hong and Dr. Vickery are optimistic about potential options in the pipeline.
“We’re just on the brink of really exciting therapies coming forward in the future,” Dr. Hong said.
The study was supported by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of the National Institutes of Health; the Claudia and Steve Stange Family Fund; Genentech; and Novartis. Dr. Hong, Dr. Kim, and Dr. Vickery reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
5 Interesting Neurology Studies
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
Long COVID
I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.
There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.
Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
Parkinson’s Classification
Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.
The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.
On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
Niemann-Pick Disease
My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.
The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
Anticoagulation in Subclinical AF
My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.
After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
Migraine and Depression
My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.
They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.
What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.
Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.
A version of this article appeared on Medscape.com.
Patient-Reported Outcomes Predict Mortality in Cutaneous Chronic GVHD
. Independent of potential confounders, these PROs moreover predicted non-relapse mortality for all three disease subtypes, making PROs potentially useful adjuncts for risk stratification and treatment decisions, the study authors said.
“These two findings highlight the importance of patient-reported outcomes in measuring this disease,” lead author Emily Baumrin, MD, MSCE, assistant professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, told this news organization. The study was published online February 28 in JAMA Dermatology.
Symptoms and QOL
The investigators monitored 436 patients from the Chronic GVHD Consortium until December 2020. The Lee Symptom Scale (LSS) skin subscale was used to evaluate symptom burden and the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) was used to measure quality of life.
Patients with sclerotic GVHD and combination disease at diagnosis had significantly worse median LSS scores than did those with epidermal disease (25, 35, and 20 points, respectively; P = .01). Patients with sclerotic disease had worse median FACT-BMT scores versus those with epidermal involvement (104 versus 109 points, respectively; P = .08).
Although these scores improved with all skin subtypes, LSS skin subscale and FACT-BMT scores remained significantly worse (by 9.0 points and 6.1 points, respectively) for patients with combination and sclerotic disease versus those with epidermal disease after adjusting for potential confounders.
Regarding mortality, every 7-point worsening (clinically meaningful difference) in FACT-BMT score at diagnosis of skin chronic GVHD conferred 9.1% increases in odds of both all-cause mortality and non-relapse mortality, after adjustment for factors such as age and sex. Likewise, for every 11 points worsening (clinically meaningful difference) in LSS skin subscale scores at diagnosis, researchers observed odds increases of 10% in all-cause mortality and 16.4% in non-relapse mortality.
Because patients with combination disease had only slightly more epidermal body surface area (BSA) involvement but significantly higher symptom burden than the other subtypes, the authors added, combination disease may represent a distinct phenotype. “Since we’ve also shown that the severity of patient-reported outcomes is associated with mortality,” Dr. Baumrin said in the interview, “perhaps these patients are at the highest risk of mortality as well.”
A growing population
Although many might think of chronic GVHD as rare, she noted, the number of allogeneic hematopoietic cell transplant (HCT) survivors living in the United States is growing. In a modeling study published in October of 2013 in Biology of Blood and Marrow Transplantation, authors predicted that by 2030, this figure will reach 502,000 — about half of whom will develop chronic GVHD, she said.
With more HCTs being performed each year and ongoing improvements in supportive care, patients are living longer post transplant. “Therefore, many transplant survivors are being taken care of in the community outside of transplant centers.”
Accordingly, Dr. Baumrin said, study findings are relevant to dermatologists in academic and transplant centers and the community who provide skin cancer screenings or other dermatologic care for transplant recipients. “Upon diagnosis of chronic GVHD, the evaluation of disease burden by patient-reported outcome measures may assist in assessing disease severity and response to treatments over time — and to stratify patients at higher risk for mortality and communicate that back to transplant physicians.”
Incorporating PROs into clinical practice might prove especially helpful for patients with sclerotic chronic cutaneous GVHD. Currently, clinicians assess cutaneous GVHD clinically, using parameters including skin thickness. The National Institutes of Health (NIH) Skin Score, used in clinical trials, also measures BSA.
“The issue with sclerosis is, it’s hard to determine clinical severity based on physical examination alone,” Dr. Baumrin said. It can be difficult to quantify skin thickness and changes over time. “So it’s hard to detect improvements, which are often slow. Patient-reported outcome measures may be a more sensitive way to detect response to treatment than our clinical assessments, which are often crude for sclerotic disease.”
In a secondary analysis of the phase 2 clinical trial of belumosudil, a treatment for chronic GVHD, published in October 2022 in Transplantation and Cellular Therapy, response rate was around 30% measured by NIH Skin Score and 77% by PROs. “Our clinical examination in sclerotic type disease falls short in terms of determining therapeutic benefit. PROs might complement those clinical measures,” she said.
Future research will involve determining and validating which PROs matter most clinically and to patients, added Dr. Baumrin. Although widely used in evaluating transplant patients, LSS skin subscale and FACT-BMT scores may not represent patients’ experience of living with cutaneous chronic GVHD as effectively as might other tools such as the Dermatology Life Quality Index (DLQI) or Patient-Reported Outcomes Measurement Information System (PROMIS) measures, she explained.
Study strengths included authors’ use of well-validated PROs rather than novel unvalidated measures, Sandra A. Mitchell, PhD, CRNP, of the National Cancer Institute, Rockville, Maryland, and Edward W. Cowen, MD, MHSc, of the Dermatology Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, Maryland, wrote in an accompanying editorial in JAMA Dermatology. However, they added, incorporating causes of death might have revealed that the excess mortality associated with sclerotic disease stemmed at least partly from adverse effects of prolonged immunosuppression, particularly infection.
If future studies establish this to be the case, said Dr. Baumrin, reducing immunosuppression might be warranted for these patients. “And if death is primarily due to chronic GVHD itself, maybe we should treat more aggressively. PROs can help guide this decision.”
The study was supported by the NIH/NIAMS and the University of Pennsylvania. Dr. Baumrin and three coauthors report no relevant financial relationships; other authors had disclosures related to several pharmaceutical companies. Dr. Mitchell and Dr. Cowen had no disclosures.
. Independent of potential confounders, these PROs moreover predicted non-relapse mortality for all three disease subtypes, making PROs potentially useful adjuncts for risk stratification and treatment decisions, the study authors said.
“These two findings highlight the importance of patient-reported outcomes in measuring this disease,” lead author Emily Baumrin, MD, MSCE, assistant professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, told this news organization. The study was published online February 28 in JAMA Dermatology.
Symptoms and QOL
The investigators monitored 436 patients from the Chronic GVHD Consortium until December 2020. The Lee Symptom Scale (LSS) skin subscale was used to evaluate symptom burden and the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) was used to measure quality of life.
Patients with sclerotic GVHD and combination disease at diagnosis had significantly worse median LSS scores than did those with epidermal disease (25, 35, and 20 points, respectively; P = .01). Patients with sclerotic disease had worse median FACT-BMT scores versus those with epidermal involvement (104 versus 109 points, respectively; P = .08).
Although these scores improved with all skin subtypes, LSS skin subscale and FACT-BMT scores remained significantly worse (by 9.0 points and 6.1 points, respectively) for patients with combination and sclerotic disease versus those with epidermal disease after adjusting for potential confounders.
Regarding mortality, every 7-point worsening (clinically meaningful difference) in FACT-BMT score at diagnosis of skin chronic GVHD conferred 9.1% increases in odds of both all-cause mortality and non-relapse mortality, after adjustment for factors such as age and sex. Likewise, for every 11 points worsening (clinically meaningful difference) in LSS skin subscale scores at diagnosis, researchers observed odds increases of 10% in all-cause mortality and 16.4% in non-relapse mortality.
Because patients with combination disease had only slightly more epidermal body surface area (BSA) involvement but significantly higher symptom burden than the other subtypes, the authors added, combination disease may represent a distinct phenotype. “Since we’ve also shown that the severity of patient-reported outcomes is associated with mortality,” Dr. Baumrin said in the interview, “perhaps these patients are at the highest risk of mortality as well.”
A growing population
Although many might think of chronic GVHD as rare, she noted, the number of allogeneic hematopoietic cell transplant (HCT) survivors living in the United States is growing. In a modeling study published in October of 2013 in Biology of Blood and Marrow Transplantation, authors predicted that by 2030, this figure will reach 502,000 — about half of whom will develop chronic GVHD, she said.
With more HCTs being performed each year and ongoing improvements in supportive care, patients are living longer post transplant. “Therefore, many transplant survivors are being taken care of in the community outside of transplant centers.”
Accordingly, Dr. Baumrin said, study findings are relevant to dermatologists in academic and transplant centers and the community who provide skin cancer screenings or other dermatologic care for transplant recipients. “Upon diagnosis of chronic GVHD, the evaluation of disease burden by patient-reported outcome measures may assist in assessing disease severity and response to treatments over time — and to stratify patients at higher risk for mortality and communicate that back to transplant physicians.”
Incorporating PROs into clinical practice might prove especially helpful for patients with sclerotic chronic cutaneous GVHD. Currently, clinicians assess cutaneous GVHD clinically, using parameters including skin thickness. The National Institutes of Health (NIH) Skin Score, used in clinical trials, also measures BSA.
“The issue with sclerosis is, it’s hard to determine clinical severity based on physical examination alone,” Dr. Baumrin said. It can be difficult to quantify skin thickness and changes over time. “So it’s hard to detect improvements, which are often slow. Patient-reported outcome measures may be a more sensitive way to detect response to treatment than our clinical assessments, which are often crude for sclerotic disease.”
In a secondary analysis of the phase 2 clinical trial of belumosudil, a treatment for chronic GVHD, published in October 2022 in Transplantation and Cellular Therapy, response rate was around 30% measured by NIH Skin Score and 77% by PROs. “Our clinical examination in sclerotic type disease falls short in terms of determining therapeutic benefit. PROs might complement those clinical measures,” she said.
Future research will involve determining and validating which PROs matter most clinically and to patients, added Dr. Baumrin. Although widely used in evaluating transplant patients, LSS skin subscale and FACT-BMT scores may not represent patients’ experience of living with cutaneous chronic GVHD as effectively as might other tools such as the Dermatology Life Quality Index (DLQI) or Patient-Reported Outcomes Measurement Information System (PROMIS) measures, she explained.
Study strengths included authors’ use of well-validated PROs rather than novel unvalidated measures, Sandra A. Mitchell, PhD, CRNP, of the National Cancer Institute, Rockville, Maryland, and Edward W. Cowen, MD, MHSc, of the Dermatology Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, Maryland, wrote in an accompanying editorial in JAMA Dermatology. However, they added, incorporating causes of death might have revealed that the excess mortality associated with sclerotic disease stemmed at least partly from adverse effects of prolonged immunosuppression, particularly infection.
If future studies establish this to be the case, said Dr. Baumrin, reducing immunosuppression might be warranted for these patients. “And if death is primarily due to chronic GVHD itself, maybe we should treat more aggressively. PROs can help guide this decision.”
The study was supported by the NIH/NIAMS and the University of Pennsylvania. Dr. Baumrin and three coauthors report no relevant financial relationships; other authors had disclosures related to several pharmaceutical companies. Dr. Mitchell and Dr. Cowen had no disclosures.
. Independent of potential confounders, these PROs moreover predicted non-relapse mortality for all three disease subtypes, making PROs potentially useful adjuncts for risk stratification and treatment decisions, the study authors said.
“These two findings highlight the importance of patient-reported outcomes in measuring this disease,” lead author Emily Baumrin, MD, MSCE, assistant professor of dermatology and medicine at the University of Pennsylvania, Philadelphia, told this news organization. The study was published online February 28 in JAMA Dermatology.
Symptoms and QOL
The investigators monitored 436 patients from the Chronic GVHD Consortium until December 2020. The Lee Symptom Scale (LSS) skin subscale was used to evaluate symptom burden and the Functional Assessment of Cancer Therapy–Bone Marrow Transplantation (FACT-BMT) was used to measure quality of life.
Patients with sclerotic GVHD and combination disease at diagnosis had significantly worse median LSS scores than did those with epidermal disease (25, 35, and 20 points, respectively; P = .01). Patients with sclerotic disease had worse median FACT-BMT scores versus those with epidermal involvement (104 versus 109 points, respectively; P = .08).
Although these scores improved with all skin subtypes, LSS skin subscale and FACT-BMT scores remained significantly worse (by 9.0 points and 6.1 points, respectively) for patients with combination and sclerotic disease versus those with epidermal disease after adjusting for potential confounders.
Regarding mortality, every 7-point worsening (clinically meaningful difference) in FACT-BMT score at diagnosis of skin chronic GVHD conferred 9.1% increases in odds of both all-cause mortality and non-relapse mortality, after adjustment for factors such as age and sex. Likewise, for every 11 points worsening (clinically meaningful difference) in LSS skin subscale scores at diagnosis, researchers observed odds increases of 10% in all-cause mortality and 16.4% in non-relapse mortality.
Because patients with combination disease had only slightly more epidermal body surface area (BSA) involvement but significantly higher symptom burden than the other subtypes, the authors added, combination disease may represent a distinct phenotype. “Since we’ve also shown that the severity of patient-reported outcomes is associated with mortality,” Dr. Baumrin said in the interview, “perhaps these patients are at the highest risk of mortality as well.”
A growing population
Although many might think of chronic GVHD as rare, she noted, the number of allogeneic hematopoietic cell transplant (HCT) survivors living in the United States is growing. In a modeling study published in October of 2013 in Biology of Blood and Marrow Transplantation, authors predicted that by 2030, this figure will reach 502,000 — about half of whom will develop chronic GVHD, she said.
With more HCTs being performed each year and ongoing improvements in supportive care, patients are living longer post transplant. “Therefore, many transplant survivors are being taken care of in the community outside of transplant centers.”
Accordingly, Dr. Baumrin said, study findings are relevant to dermatologists in academic and transplant centers and the community who provide skin cancer screenings or other dermatologic care for transplant recipients. “Upon diagnosis of chronic GVHD, the evaluation of disease burden by patient-reported outcome measures may assist in assessing disease severity and response to treatments over time — and to stratify patients at higher risk for mortality and communicate that back to transplant physicians.”
Incorporating PROs into clinical practice might prove especially helpful for patients with sclerotic chronic cutaneous GVHD. Currently, clinicians assess cutaneous GVHD clinically, using parameters including skin thickness. The National Institutes of Health (NIH) Skin Score, used in clinical trials, also measures BSA.
“The issue with sclerosis is, it’s hard to determine clinical severity based on physical examination alone,” Dr. Baumrin said. It can be difficult to quantify skin thickness and changes over time. “So it’s hard to detect improvements, which are often slow. Patient-reported outcome measures may be a more sensitive way to detect response to treatment than our clinical assessments, which are often crude for sclerotic disease.”
In a secondary analysis of the phase 2 clinical trial of belumosudil, a treatment for chronic GVHD, published in October 2022 in Transplantation and Cellular Therapy, response rate was around 30% measured by NIH Skin Score and 77% by PROs. “Our clinical examination in sclerotic type disease falls short in terms of determining therapeutic benefit. PROs might complement those clinical measures,” she said.
Future research will involve determining and validating which PROs matter most clinically and to patients, added Dr. Baumrin. Although widely used in evaluating transplant patients, LSS skin subscale and FACT-BMT scores may not represent patients’ experience of living with cutaneous chronic GVHD as effectively as might other tools such as the Dermatology Life Quality Index (DLQI) or Patient-Reported Outcomes Measurement Information System (PROMIS) measures, she explained.
Study strengths included authors’ use of well-validated PROs rather than novel unvalidated measures, Sandra A. Mitchell, PhD, CRNP, of the National Cancer Institute, Rockville, Maryland, and Edward W. Cowen, MD, MHSc, of the Dermatology Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, Maryland, wrote in an accompanying editorial in JAMA Dermatology. However, they added, incorporating causes of death might have revealed that the excess mortality associated with sclerotic disease stemmed at least partly from adverse effects of prolonged immunosuppression, particularly infection.
If future studies establish this to be the case, said Dr. Baumrin, reducing immunosuppression might be warranted for these patients. “And if death is primarily due to chronic GVHD itself, maybe we should treat more aggressively. PROs can help guide this decision.”
The study was supported by the NIH/NIAMS and the University of Pennsylvania. Dr. Baumrin and three coauthors report no relevant financial relationships; other authors had disclosures related to several pharmaceutical companies. Dr. Mitchell and Dr. Cowen had no disclosures.
FROM JAMA DERMATOLOGY
AAP Updates Guidance on Vaccine Communication and Hesitancy
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
The measles outbreak in Florida, occurring just as health officials announced an official end to Philadelphia’s measles outbreak and rising global cases, has cast attention once again on concerns about vaccine hesitancy. In the midst of Florida’s surgeon general avoiding measles vaccination recommendations for parents, the American Academy of Pediatrics has updated its clinical guidance on vaccine communication.
“Disruption to routine pediatric vaccination during the COVID-19 pandemic has left many children vulnerable to vaccine-preventable diseases and more locations susceptible to outbreaks in the United States and around the world,” Sean T. O’Leary, MD, MPH, a pediatric infectious diseases specialist and associate professor of pediatrics at the University of Colorado in Aurora, and his colleagues, wrote in the new report, published in the March issue of Pediatrics. “Geographic clustering of vaccine refusal further increases the risk of communicable disease outbreaks in certain communities even when vaccination rates at a state or national level remain high overall.”
The authors note that disease resurgence may bolster vaccine uptake, with media coverage of recent outbreaks linked to more pro-vaccine discussions and attitudes among parents. But the evidence on that remains inconclusive, and the authors point out the slow uptake in COVID-19 vaccination as parents navigate ongoing spread of both the disease and vaccine misinformation.
Conflicting Evidence on Postpandemic Attitudes
It remains unclear how parent attitudes toward vaccines have shifted, if at all, since the pandemic. A study published in Pediatrics from October 2023, which Dr. O’Leary also coauthored, analyzed data from an online survey of Colorado mothers between 2018 and 2021 and found no significant difference in vaccine hesitancy during the pandemic compared with pre-pandemic.
Among 3,553 respondents, 1 in 5 (20.4%) were vaccine hesitant overall. Though parents were twice as likely to feel uncertain in trusting vaccine information after the COVID-19 vaccines were authorized (adjusted odds ratio [aOR] 2.14), they were half as likely to be unsure about hesitancy toward childhood vaccines (aOR 0.48).
Another study in Pediatrics from October 2023 found that common concerns about COVID-19 vaccines among parents included infertility, long-term effects from the vaccines, and effects on preexisting medical conditions. But even then, participants in focus groups “expressed that they would listen to their doctor for information about COVID-19 vaccines,” wrote Aubree Honcoop, MPS, of the University of Nebraska Medical Center in Omaha, and her colleagues.
“I think what we’re seeing, very importantly, is that physicians seem to be the source people rely on,” said Walter Orenstein, MD, professor of medicine and associate director of the Emory Vaccine Center at Emory University in Atlanta. “But we need to give the physicians time and incentives to spend time with families,” such as a billing code for vaccine counseling, he said.
Dr. Orenstein was surprised to see the results from Colorado, but he noted they were from a small survey in a single state. He pointed to other findings, such as those from the University of Pennsylvania’s Annenberg Public Policy Center in November 2023, that found lower confidence overall among Americans toward vaccines.
Paul Offit, MD, director of the Vaccine Education Center and an attending infectious disease physician at Children’s Hospital of Philadelphia, where the city’s measles outbreak began, is similarly skeptical about the Colorado study’s findings that parent vaccine attitudes have changed little since the pandemic. At the AAP’s annual conference in October 2023, Dr. Offit asked pediatricians about their experiences while he signed books.
“I would ask, ‘So what’s it like out there? Are we winning or losing?’ ” he said. “I would say, to a person, everyone said they felt things were much worse now than they ever have been before.”
Clinical Guidance
The new report reviews previously published evidence on the spectrum of parental vaccine acceptance — from supporters and “go along to get along” parents to cautious acceptors and fence sitters to vaccine refusers — and the determinants that contribute to hesitancy. They also noted the social inequities that have played a role in vaccine uptake disparities.
“Distrust of health systems based on historic and ongoing discrimination and inequitable access to care are intertwined challenges that contribute to racial and ethnic disparities in vaccine uptake,” the authors wrote. “Although there has been progress in reducing racial, ethnic, and socioeconomic disparities in childhood vaccination coverage, the COVID-19 pandemic made clear how much work is yet to be done.”
The report also reviewed the societal, individual, payer and pediatric practice costs of vaccine refusal. The 1-year cost to taxpayers from the measles outbreak in New York City in 2018-2019, for example, was $8.4 million, excluding vaccination programs.
The report provides background information to equip pediatricians for conversations with parents about vaccines. Since safety is the top concern for vaccine hesitancy among parents, the authors advised pediatricians to be familiar with the process of vaccine testing, emergency use authorization, licensure, approval, recommendations, and safety monitoring, including the Vaccine Safety Datalink, the Vaccine Adverse Event Reporting System (VAERS), the FDA’s Biologics Effectiveness and Safety (BEST) system, and the CDC’s Clinical Immunization Safety Assessment Project (CISA).
“Because vaccines are generally given to healthy individuals to prevent disease, they are held to a higher safety standard than other medications,” the authors wrote before providing a summary of the process for physicians to reference. The report also includes information on vaccine ingredients and a chart of common misconceptions about vaccines with the corresponding facts.
Overcoming Hesitancy
Evidence-based strategies for increasing childhood vaccine uptake begin with a strong vaccine recommendation using a presumptive rather than participatory approach, the authors wrote. “A presumptive format is one in which the clinician asserts a position regarding vaccines using a closed-ended statement, such as ‘Sara is due for several vaccines today’ or ‘Well, we have to do some shots,’ ” the authors wrote. “This strategy is in contrast to a participatory format, in which an open-ended question is used to more explicitly invite the parent to voice an opinion, such as ‘How do you feel about vaccines today?’ ” The presumptive format and a strong recommendation are both associated with greater uptake, evidence shows.
For parents who express hesitancy, the authors provide a summary of additional evidence-based communication strategies, starting with motivational interviewing. Two other strategies they highlight include using language to re-emphasize the importance of adhering to the CDC recommended schedule — “He really needs these shots” — and bundling discussion of all recommended vaccines for a visit at once.
“Finally, clinicians can emphasize their own experiences when discussing the need for vaccination, including personal experience with vaccine-preventable diseases and the fact that they and their families are vaccinated because of their confidence in the safety and efficacy of the vaccines,” the authors wrote.
For families who refuse or delay vaccines, the authors reviewed the “ethical arguments both in favor of and against dismissal policies,” noting that nearly all pediatricians who report dismissing families who refuse vaccination are in private practice, since large systems are often unable to dismiss patients. They also point out that fewer pediatricians dismiss families for spreading out vaccines than outright refusing all vaccines.
”Dismissal of child patients of vaccine-refusing parents can be a difficult decision arrived at after considering multiple factors and documented attempts to counsel vaccine-refusing families,” they wrote. “However, if repeated attempts to help understand and address parental values and vaccine concerns fails to engender trust, move parents toward vaccine acceptance, or strengthen the therapeutic alliance, dismissal can be an acceptable option.”
Finally, the authors reminded pediatricians “that vaccine-hesitant parents are a heterogeneous group and that specific parental vaccine concerns need to be individually identified and addressed.” Working with families to discuss their questions and concerns is an opportunity to “build rapport and trust with a family,” they wrote, ”and, ultimately, protect their children from the scourge of vaccine-preventable diseases.”
The focus groups study was funded by the National Institutes of Health, and the authors reported having no disclosures. The Colorado attitudes study used no external funding, and the authors reported no disclosures. The new clinical report used no external funding, and the authors reported no disclosures. Dr. Orenstein is an uncompensated member of the Moderna Scientific Advisory Board. Dr. Offit codeveloped a licensed rotavirus vaccine, but he does not receive any royalties or own a patent for that.
FROM PEDIATRICS