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What is the dark side of GLP-1 receptor agonists?
The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however,
“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.
Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.
GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
Severe Gastric Problems
A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.
There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.
These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
Anesthetic Complications
In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.
Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.
The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.
Increased Suicidality Risk?
In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.
Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
Long-Term Safety
GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.
Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.
With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
Awaiting Guideline Updates
Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.
The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however,
“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.
Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.
GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
Severe Gastric Problems
A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.
There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.
These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
Anesthetic Complications
In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.
Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.
The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.
Increased Suicidality Risk?
In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.
Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
Long-Term Safety
GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.
Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.
With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
Awaiting Guideline Updates
Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.
The approval of the GLP-1 receptor agonist semaglutide for weight regulation in January 2023 ushered in a new era of obesity therapy. In recent months, however,
“When millions of people are treated with medications like semaglutide, even relatively rare side effects occur in a large number of individuals,” Susan Yanovski, MD, codirector of the Office of Obesity Research at the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Maryland, said in a JAMA news report.
Despite the low incidence of these adverse events and the likelihood that the benefits outweigh these risks in individuals with severe obesity, doctors and patients should be aware of these serious side effects, she added.
GLP-1 receptor agonists like semaglutide or liraglutide mimic certain intestinal hormones. Almost all their characteristic side effects involve the gastrointestinal tract: nausea, vomiting, constipation, and diarrhea. However, these are not the rare, severe side effects that are gaining increasing attention.
Severe Gastric Problems
A recent analysis published in JAMA shows that GLP-1 receptor agonists are associated with a ninefold higher risk of pancreatitis, compared with bupropion, an older weight-loss medication. Patients receiving GLP-1 receptor agonists also had four times more frequent intestinal obstruction and more than three times more frequent gastroparesis. The absolute risks for these complications, however, were less than 1% per year of use.
There were no indications of an increased risk for gallbladder diseases. Acute pancreatitis and acute gallbladder diseases are known complications of GLP-1 receptor agonists.
These results “reinforce that these are effective medications, and all medications have side effects,” said Dr. Yanovski. She emphasized that despite a significant increase in relative risk, however, the absolute risk remains very low.
Anesthetic Complications
In the spring of 2023, reports of patients taking GLP-1 receptor agonists and vomiting or aspirating food during anesthesia surfaced in some scientific journals. It was particularly noticeable that some of these patients vomited unusually large amounts of stomach contents, even though they had not eaten anything, as directed by the doctor before the operation.
Experts believe that the slowed gastric emptying intentionally caused by GLP-1 receptor agonists could be responsible for these problems.
The American Society of Anesthesiologists now recommends that patients do not take GLP-1 receptor agonists on the day of surgery and discontinue weekly administered agents like Wegovy 7 days before the procedure.
Increased Suicidality Risk?
In July, case reports of depression and suicidal ideation led the European Medicines Agency to investigate about 150 cases of potential self-harm and suicidal thoughts in patients who had received liraglutide or semaglutide. The review now also includes other GLP-1 receptor agonists. Results of the review process are expected in December.
Dr. Yanovski noted that it is unclear whether these incidents are caused by the drugs, but suicidal thoughts and suicidal behavior have also been observed with other medications for obesity treatment (eg, rimonabant). “It is certainly a good idea to use these medications cautiously in patients with a history of suicidality and monitor the patients accordingly,” she said.
Long-Term Safety
GLP-1 receptor agonists likely need to be used long term, potentially for life, for the effects on body weight to persist. Whether there are side effects and complications that only become apparent over time is currently unknown — especially when these medications are used for weight reduction.
Studies in rodents have suggested an increased risk of medullary thyroid carcinomas. Whether a similar signal exists in humans may only become apparent in many years. In patients who have had medullary thyroid carcinoma themselves or in the family, dulaglutide, liraglutide, semaglutide, and tirzepatide, a dual GLP-1/GIP receptor agonist, are contraindicated.
With dual agonists like tirzepatide or even triple agonists like retatrutide (GLP-1/GIP/glucagon), patients can lose significantly more weight than with the monoagonist semaglutide. Gastrointestinal events were also frequent in studies of dual agonists.
Awaiting Guideline Updates
Guidelines for using these new medications are still scarce. “There are clinical guidelines for obesity therapy, but they were all written before the GLP-1 receptor agonists came on the market,” said Dr. Yanovski. “Medical societies are currently working intensively to develop new guidelines to help doctors use these medications safely and effectively in clinical practice.”
This article was translated from the Medscape German edition. A version of this article appeared on Medscape.com.
FROM JAMA
Which factors distinguish superagers from the rest of us?
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Even at an advanced age, superagers have the memory of someone 20 or 30 years their junior. But why is that? A new study shows that, in superagers, However, the study also emphasizes the importance of physical and mental fitness for a healthy aging process.
“One of the most important unanswered questions with regard to superagers is: ‘Are they resistant to age-related memory loss, or do they have coping mechanisms that allow them to better offset this memory loss?’ ” wrote Marta Garo-Pascual, a PhD candidate at the Autonomous University of Madrid, Spain, and colleagues in the Lancet Healthy Longevity. “Our results indicate that superagers are resistant to these processes.”
Six years’ monitoring
From a cohort of older adults who had participated in a study aiming to identify early indicators of Alzheimer’s disease, the research group chose 64 superagers and 55 normal senior citizens. The latter served as the control group. While the superagers performed just as well in a memory test as people 30 years their junior, the control group’s performance was in line with their age and level of education.
All study participants were over age 79 years. Both the group of superagers and the control group included more females than males. On average, they were monitored for 6 years. During this period, a checkup was scheduled annually with an MRI examination, clinical tests, blood tests, and documentation of lifestyle factors.
For Alessandro Cellerino, PhD, of the Leibniz Institute on Aging–Fritz Lipmann Institute in Jena, Germany, this is the most crucial aspect of the study. “Even before this study, we knew that superagers demonstrated less atrophy in certain areas of the brain, but this was always only ever based on a single measurement.”
Memory centers protected
The MRI examinations confirmed that in superagers, gray matter atrophy in the regions responsible for memory (such as the medial temporal lobe and cholinergic forebrain), as well in regions important for movement (such as the motor thalamus), was less pronounced. In addition, the volume of gray matter in these regions, especially in the medial temporal lobe, decreased much more slowly in the superagers than in the control subjects over the study period.
Ms. Garo-Pascual and associates used a machine-learning algorithm to differentiate between superagers and normal older adults. From the 89 demographic, lifestyle, and clinical factors entered into the algorithm, two were the most important for the classification: the ability to move and mental health.
Mobility and mental health
Clinical tests such as the Timed Up-and-Go Test and the Finger Tapping Test revealed that superagers can be distinguished from the normally aging control subjects with regard to their mobility and fine motor skills. Their physical condition was better, although they, by their own admission, did not move any more than the control subjects in day-to-day life. According to Dr. Cellerino, this finding confirms that physical activity is paramount for cognitive function. “These people were over 80 years old – the fact that there was not much difference between their levels of activity is not surprising. Much more relevant is the question of how you get there – i.e., how active you are at the ages of 40, 50 or even 60 years old.”
Remaining active is important
As a matter of fact, the superagers indicated that generally they had been more active than the control subjects during their middle years. “Attempting to stay physically fit is essential; even if it just means going for a walk or taking the stairs,” said Dr. Cellerino.
On average, the superagers also fared much better in tests on physical health than the control subjects. They suffered significantly less from depression or anxiety disorders. “Earlier studies suggest that depression and anxiety disorders may influence performance in memory tests across all ages and that they are risk factors for developing dementia,” said Dr. Cellerino.
To avoid mental health issues in later life, gerontologist Dr. Cellerino recommended remaining socially engaged and involved. “Depression and anxiety are commonly also a consequence of social isolation,” he said.
Potential genetic differences
Blood sample analyses demonstrated that the superagers exhibited lower concentrations of biomarkers for neurodegenerative diseases than the control group did. In contrast, there was no difference between the two groups in the prevalence of the apo e4 allele, one of the most important genetic risk factors for Alzheimer’s disease. Nevertheless, Ms. Garo-Pascual and associates assume that genetics also play a role. They found that, despite 89 variables employed, the algorithm used could only distinguish superagers from normal older adults 66% of the time. This suggests that additional factors must be in play, such as genetic differences.
Body and mind
Since this is an observational study, whether the determined factors have a direct effect on superaging cannot be ascertained, the authors wrote. However, the results are consistent with earlier findings.
“Regarding the management of old age, we actually haven’t learned anything more than what we already knew. But it does confirm that physical and mental function are closely entwined and that we must maintain both to age healthily,” Dr. Cellerino concluded.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
FROM THE LANCET HEALTHY LONGEVITY
What causes sudden cardiac arrest in young people?
Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.
Recognizing warning signs
Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:
- Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
- Seizures without a clear pathologic EEG result (for example, epilepsy)
- Unexplained accidents or car crashes
- Heart failure or pacemaker dependency before age 50 years
“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
Sports rarely responsible
Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.
“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
Inherited disorders
The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.
Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
Testing of family
“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.
In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
Lack of knowledge
Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”
For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.
Recognizing warning signs
Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:
- Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
- Seizures without a clear pathologic EEG result (for example, epilepsy)
- Unexplained accidents or car crashes
- Heart failure or pacemaker dependency before age 50 years
“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
Sports rarely responsible
Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.
“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
Inherited disorders
The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.
Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
Testing of family
“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.
In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
Lack of knowledge
Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”
For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Sudden cardiac arrest is the term given to death that results from a cardiac cause and occurs within an hour of symptoms being observed. If no witnesses are present, sudden cardiac arrest is present if the person had been in apparently good health 24 hours before cardiac death. Fatality is usually a result of sustained ventricular fibrillation or sustained ventricular tachycardia that leads to cardiac arrest.
Recognizing warning signs
Warning signs that should prompt physicians to consider an increased risk of sudden cardiac arrest include the following:
- Unexplained, brief fainting episodes that above all occur with stress, physical activity, or loud noises (for example, alarm ringing)
- Seizures without a clear pathologic EEG result (for example, epilepsy)
- Unexplained accidents or car crashes
- Heart failure or pacemaker dependency before age 50 years
“These are all indications that could point to an underlying heart disease that should be investigated by a medical professional,” explained Silke Kauferstein, PhD, head of the Center for Sudden Cardiac Arrest and Familial Arrhythmia Syndrome at the Institute of Forensic Medicine of the University Frankfurt am Main (Germany), in a podcast by the German Heart Foundation.
Sports rarely responsible
Sudden cardiac arrest has numerous causes. Sudden cardiac arrests in a professional sports environment always attract attention. Yet sports play a less important role in sudden cardiac arrest than is often assumed, even in young individuals.
“The incidence of sudden cardiac arrest is on average 0.7-3 per 100,000 sports players from all age groups,” said Thomas Voigtländer, MD, chair of the German Heart Foundation, in an interview. Men make up 95% of those affected, and 90% of these events occur during recreational sports.
Inherited disorders
The most significant risk factor for sudden cardiac arrest is age; it is often associated with coronary heart disease. This factor can be significant from as early as age 35 years. Among young individuals, sudden cardiac arrest is often a result of congenital heart diseases, such as hypertrophic cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy. Diseases such as long QT syndrome and Brugada syndrome can also lead to sudden cardiac arrest.
Among young sports players who experience sudden cardiac arrest, the cause is often an overlooked hereditary factor. “Cardiac screening is recommended in particular for young, high-performance athletes from around 14 years old,” said Dr. Voigtländer, who is also a cardiologist and medical director of the Agaplesion Bethanien Hospital in Frankfurt.
Testing of family
“If sudden cardiac arrest or an unexplained sudden death occurs at a young age in the family, the primary care practitioner must be aware that this could be due to heart diseases that could affect the rest of the family,” said Dr. Voigtländer.
In these cases, primary care practitioners must connect the other family members to specialist outpatient departments that can test for genetic factors, he added. “Many of these genetic diseases can be treated successfully if they are diagnosed promptly.”
Lack of knowledge
Dr. Kauferstein, who runs such a specialist outpatient department, said, “unfortunately, many affected families do not know that they should be tested as well. This lack of knowledge can also lead to fatal consequences for relatives.”
For this reason, she believes that it is crucial to provide more information to the general population. Sudden cardiac arrest is often the first sign of an underlying heart disease in young, healthy individuals. “We do see warning signals in our in-depth testing of sudden cardiac arrest cases that have often been overlooked,” said Dr. Kauferstein.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Is education or screening better for type 1 diabetes?
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.
After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. at the Diabetes Congress in Berlin.
Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
Two autoantibodies
One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”
The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:
- Early stage 1: Two or more islet autoantibodies and normoglycemia.
- Early stage 2: Two or more islet autoantibodies and dysglycemia.
- Early stage 3: Symptoms, hyperglycemia, insulin therapy.
The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
Education and care
The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.
The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.
“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”
The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
Dubious benefits?
The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.
In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.
Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
Severe side effects
Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.
“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
Education reduces ketoacidosis
“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.
Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.
Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.
“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
New therapeutic options
Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.
For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”
This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.
Women with cycle disorders across their life span may be at increased risk of cardiovascular disease
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
This finding is demonstrated in a new analysis of the Nurses’ Health Study II.
“To date, several studies have reported increased risks of cardiovascular risk factors or cardiovascular disease in connection with cycle disorders,” Yi-Xin Wang, MD, PhD, a research fellow in nutrition, and associates from the Harvard School of Public Health, Boston, wrote in an article published in JAMA Network Open.
Ute Seeland, MD, speaker of the Gender Medicine in Cardiology Working Group of the German Cardiology Society, said in an interview“We know that women who have indicated in their medical history that they have irregular menstrual cycles, invariably in connection with polycystic ovary syndrome (PCOS), more commonly develop diabetes and other metabolic disorders, as well as cardiovascular diseases.”
Cycle disorders’ role
However, the role that irregular or especially long cycles play at different points of a woman’s reproductive life span was unclear. Therefore, the research group investigated the associations in the Nurses’ Health Study II between cycle irregularity and cycle length in women of different age groups who later experienced cardiovascular events.
At the end of this study in 1989, the participants also provided information regarding the length and irregularity of their menstrual cycle from ages 14 to 17 years and again from ages 18 to 22 years. The information was updated in 1993 when the participants were aged 29-46 years. The data from 2019 to 2022 were analyzed.
“This kind of long-term cohort study is extremely rare and therefore something special,” said Dr. Seeland, who conducts research at the Institute for Social Medicine, Epidemiology, and Health Economics at the Charité – University Hospital Berlin.
The investigators used the following cycle classifications: very regular (no more than 3 or 4 days before or after the expected date), regular (within 5-7 days), usually irregular, always irregular, or no periods.
The cycle lengths were divided into the following categories: less than 21 days, 21-25 days, 26-31 days, 32-39 days, 40-50 days, more than 50 days, and too irregular to estimate the length.
The onset of cardiovascular diseases was determined using information from the participants and was confirmed by reviewing the medical files. Relevant to the study were lethal and nonlethal coronary heart diseases (such as myocardial infarction or coronary artery revascularization), as well as strokes.
Significant in adulthood
The data from 80,630 study participants were included in the analysis. At study inclusion, the average age of the participants was 37.7 years, and the average body mass index (BMI) was 25.1. “Since it was predominantly White nurses who took part in the study, the data are not transferable to other, more diverse populations,” said Dr. Seeland.
Over 24 years, 1,816 women (2.4%) had a cardiovascular event. “We observed an increased rate of cardiovascular events in women with an irregular cycle and longer cycle, both in early an in mid-adulthood,” wrote Dr. Wang and associates. “Similar trends were also observed for cycle disorders when younger, but this association was weaker than in adulthood.”
Compared with women with very regular cycles, women with irregular cycles or without periods who were aged 14-17 years, 18-22 years, or 29-49 years exhibited a 15%, 36%, and 40% higher risk of a cardiovascular event, respectively.
Similarly, women aged 18-22 years or 29-46 years with long cycles of 40 days or more had a 44% or 30% higher risk of cardiovascular disease, respectively, compared with women with cycle lengths of 26-31 days.
“The coronary heart diseases were decisive for the increase, and less so, the strokes,” wrote the researchers.
Classic risk factors?
Dr. Seeland praised the fact that the study authors tried to determine the role that classic cardiovascular risk factors played. “Compared with women with a regular cycle, women with an irregular cycle had a higher BMI, more frequently increased cholesterol levels, and an elevated blood pressure,” she said. Women with a long cycle displayed a similar pattern.
It can be assumed from this that over a woman’s life span, BMI affects the risk of cardiovascular disease. Therefore, Dr. Wang and coauthors adjusted the results on the basis of BMI, which varies over time.
Regarding other classic risk factors that may have played a role, “hypercholesterolemia, chronic high blood pressure, and type 2 diabetes were only responsible in 5.4%-13.5% of the associations,” wrote the researchers.
“Our results suggest that certain characteristics of the menstrual cycle across a woman’s reproductive lifespan may constitute additional risk markers for cardiovascular disease,” according to the authors.
The highest rates of cardiovascular disease were among women with permanently irregular or long cycles in early to mid adulthood, as well as women who had regular cycles when younger but had irregular cycles in mid adulthood. “This indicates that the change from one cycle phenotype to another could be a surrogate marker for metabolic changes, which in turn contribute to the formation of cardiovascular diseases,” wrote the authors.
The study was observational and so conclusions cannot be drawn regarding causal relationships. But Dr. Wang and associates indicate that the most common cause of an irregular menstrual cycle may be PCOS. “Roughly 90% of women with cycle disorders or oligomenorrhea have signs of PCOS. And it was shown that women with PCOS have an increased risk of cardiovascular disease.”
They concluded that “the associations observed between irregular and long cycles in early to mid-adulthood and cardiovascular diseases are likely attributable to underlying PCOS.”
For Dr. Seeland, however, this conclusion is “too monocausal. At no point in time did there seem to be any direct information regarding the frequency of PCOS during the data collection by the respondents.”
For now, we can only speculate about the mechanisms. “The association between a very irregular and long cycle and the increased risk of cardiovascular diseases has now only been described. More research should be done on the causes,” said Dr. Seeland.
This article was translated from the Medscape German edition. A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
What are the benefits of a fourth vaccination against COVID?
The fourth vaccination against COVID-19 is the subject of intense discussion. Immunity against new Omicron variants (currently BA.4 and BA.5) is getting weaker and weaker. Is another vaccination with the available vaccines worth it?
For Leif Erik Sander, MD, director of infectious diseases and pneumology at Charité University Medicine, Berlin, the latest data send a clear message. “The COVID-19 vaccination is still effective against Omicron. After three doses of the vaccine, it continues to prevent severe diseases, respiratory failures, and death,” he reported at the 62nd Congress of the German Pneumology and Respiratory Medicine Society in Leipzig.
The most recent data from the United Kingdom show that the vaccine’s effectiveness against Omicron decreases after just a few months, which speaks in favor of a fourth vaccination. “Omicron is a development that we did not anticipate occurring so early on,” said Dr. Sander.
In terms of phylogenetics, Omicron is far removed from the previous variants of concern. More than 30 mutations to the spike protein (the antigen that is vaccinated against) foster the loss of immunity.
Boosters broaden immunity
“The booster makes all the difference here,” emphasized Dr. Sander. Experiments at Charité Berlin show that after double vaccination, the vaccination sera from healthy young people no longer neutralizes Omicron.
“The third vaccination broadens the humoral immune response against the spike protein so that conserved epitopes that are unchanged, even in Omicron, are addressed, with the result that you have neutralization capacity again,” the infectious diseases specialist explained.
Continued protection
However, data from the United Kingdom on vaccine effectiveness show where the limit lies. Initially, after three doses, vaccine effectiveness against symptomatic disease after Omicron infection is very good. This effectiveness decreases significantly over the course of the next few months. “Lots of people experience an Omicron infection despite the booster,” said Mr. Sander.
Nonetheless, the high incidence of Omicron infections in the recent past has not overwhelmed the health care system. “This is because the vaccine’s effectiveness against severe diseases that require hospitalization and against respiratory failure is still good in the at-risk population over the age of 65, once they have had their three vaccinations,” said Dr. Sander. The data also show that there is good protection of over 90%, even against mortality.
Waning observed
It could be said that currently, vaccination even continues to work against Omicron, says Dr. Sander. It prevents severe disease, respiratory failure, and death. Nonetheless, after just 3 months, a slight waning of immune protection can be observed in all three endpoints.
Therefore, the question arises as to whether a fourth vaccination is worthwhile. In Israel, “Delta was successfully eradicated with the third vaccination,” and now they are trying this again for Omicron with a fourth vaccination, reported Dr. Sander.
Fourth vaccination protective
The first investigations show that protection against severe disease can be increased once more. “For the over-60s, protection is almost quadrupled through the fourth vaccination,” says Dr. Sander. “However, this is still plagued with a lot of uncertainty; it is still not known how stable it is.”
There is hope on the basis of results of an as yet non–peer-reviewed study from Sweden, which is currently available only as a preprint. That study shows that a fourth vaccination in a high-risk population of care-home residents and people older than 80 years can halve overall mortality. “If this can be confirmed and replicated, it must be recommended quite extensively for this high-risk group,” said Dr. Sander. The Standing Committee on Vaccination in Germany is currently recommending that high-risk groups be vaccinated against COVID-19 for the fourth time. To date, though, this has only been implemented halfheartedly.
Propensity for mutation
Omicron keeps developing. Following BA.1 and the more infectious subvariant BA.2, BA.4 and BA.5 are spreading in Germany. “To date, there is no evidence that vaccine protection against severe diseases has changed as a result of BA.2 emerging,” said Dr. Sander.
However, the loss of immunity against BA.4 and BA.5 is more strongly pronounced. “If you were infected with BA.1, you are not immune to BA.5,” says Dr. Sander. Lessened immunity from BA.4 and BA.5 is even more pronounced. “Anyone who was infected with BA.1 is not immune to BA.5,” says Dr. Sander. The two clades not only have spike protein mutations shared by BA.2 but also additional spike protein mutations. According to the expert, it could well be that these strains will prevail because they are best able to avoid the immunity of the population.
Adapted vaccines feasible?
“Vaccines adapted to BA.1 were developed very early on and were also part of clinical research,” said Dr. Sander. The initial data indicate that additional antibody responses are being mobilized that may neutralize the new variants.
It was deduced from trials on monkeys that the available vaccines were so good that only small improvements were to be expected, said Dr. Sander.
Moderna’s adapted vaccine
The U.S. pharmaceutical company Moderna recently submitted the first results regarding its bivalent Omicron vaccine mRNA-1273.214, which is adapted to Omicron BA.1. Data from BioNTech are expected soon.
Moderna tested a booster that contains both the spike mRNA from the original vaccine and a new mRNA adapted to the Omicron variant BA.1. The experimental vaccine mRNA-1273.214 exhibited an eightfold increase in geometric mean neutralization titer against Omicron in study participants who were seronegative at the start, compared with the already-approved vaccine.
In its latest notice, Moderna did not publish any data on how effective the updated vaccine is against the virus variants BA.4 or BA.5. Data on clinical endpoints, such as hospitalization or mortality, are also not available.
Conservative epitopes
Should it be assumed that the development of vaccines will always lag the emergence of new subvariants? In this respect, Dr. Sander appears optimistic. “The immunological mechanism is clear, that various B cells and antibodies will be formed that are directed against conservative epitopes that have various variants. This is good news, since we do not want to protect against BA.1 now, just for BA.8 to emerge when the vaccine goes to market. We want to protect ourselves as broadly as possible, and it seems like it may be possible to do so with this vaccine.”
Double vaccination?
Dr. Sander anticipates that a fourth vaccination against COVID-19 will occur with the next wave of the coronavirus in September or October. He remarked that coupling it with the influenza vaccination should be considered.
The coronavirus pandemic has led to shifts in other seasonal waves of pathogens. In the summer, pediatric departments were unexpectedly inundated with children suffering from RSV infections. And while the flu season over the past 2 years has been almost absent, the influenza wave may occur significantly earlier than usual this year.
“In Australia, the influenza wave arrived much earlier this year than usual, which may of course also be fruitful for us,” said Dr. Sander. “Perhaps we will also get influenza as early as in September or October. I would then plead for vaccine centers to be allowed to vaccinate against both influenza and COVID-19 at the same time. Maybe then we will also have a reasonable influenza vaccination rate,” he added.
This article was translated from the Medscape German edition.
A version of this article first appeared on Medscape.com.
The fourth vaccination against COVID-19 is the subject of intense discussion. Immunity against new Omicron variants (currently BA.4 and BA.5) is getting weaker and weaker. Is another vaccination with the available vaccines worth it?
For Leif Erik Sander, MD, director of infectious diseases and pneumology at Charité University Medicine, Berlin, the latest data send a clear message. “The COVID-19 vaccination is still effective against Omicron. After three doses of the vaccine, it continues to prevent severe diseases, respiratory failures, and death,” he reported at the 62nd Congress of the German Pneumology and Respiratory Medicine Society in Leipzig.
The most recent data from the United Kingdom show that the vaccine’s effectiveness against Omicron decreases after just a few months, which speaks in favor of a fourth vaccination. “Omicron is a development that we did not anticipate occurring so early on,” said Dr. Sander.
In terms of phylogenetics, Omicron is far removed from the previous variants of concern. More than 30 mutations to the spike protein (the antigen that is vaccinated against) foster the loss of immunity.
Boosters broaden immunity
“The booster makes all the difference here,” emphasized Dr. Sander. Experiments at Charité Berlin show that after double vaccination, the vaccination sera from healthy young people no longer neutralizes Omicron.
“The third vaccination broadens the humoral immune response against the spike protein so that conserved epitopes that are unchanged, even in Omicron, are addressed, with the result that you have neutralization capacity again,” the infectious diseases specialist explained.
Continued protection
However, data from the United Kingdom on vaccine effectiveness show where the limit lies. Initially, after three doses, vaccine effectiveness against symptomatic disease after Omicron infection is very good. This effectiveness decreases significantly over the course of the next few months. “Lots of people experience an Omicron infection despite the booster,” said Mr. Sander.
Nonetheless, the high incidence of Omicron infections in the recent past has not overwhelmed the health care system. “This is because the vaccine’s effectiveness against severe diseases that require hospitalization and against respiratory failure is still good in the at-risk population over the age of 65, once they have had their three vaccinations,” said Dr. Sander. The data also show that there is good protection of over 90%, even against mortality.
Waning observed
It could be said that currently, vaccination even continues to work against Omicron, says Dr. Sander. It prevents severe disease, respiratory failure, and death. Nonetheless, after just 3 months, a slight waning of immune protection can be observed in all three endpoints.
Therefore, the question arises as to whether a fourth vaccination is worthwhile. In Israel, “Delta was successfully eradicated with the third vaccination,” and now they are trying this again for Omicron with a fourth vaccination, reported Dr. Sander.
Fourth vaccination protective
The first investigations show that protection against severe disease can be increased once more. “For the over-60s, protection is almost quadrupled through the fourth vaccination,” says Dr. Sander. “However, this is still plagued with a lot of uncertainty; it is still not known how stable it is.”
There is hope on the basis of results of an as yet non–peer-reviewed study from Sweden, which is currently available only as a preprint. That study shows that a fourth vaccination in a high-risk population of care-home residents and people older than 80 years can halve overall mortality. “If this can be confirmed and replicated, it must be recommended quite extensively for this high-risk group,” said Dr. Sander. The Standing Committee on Vaccination in Germany is currently recommending that high-risk groups be vaccinated against COVID-19 for the fourth time. To date, though, this has only been implemented halfheartedly.
Propensity for mutation
Omicron keeps developing. Following BA.1 and the more infectious subvariant BA.2, BA.4 and BA.5 are spreading in Germany. “To date, there is no evidence that vaccine protection against severe diseases has changed as a result of BA.2 emerging,” said Dr. Sander.
However, the loss of immunity against BA.4 and BA.5 is more strongly pronounced. “If you were infected with BA.1, you are not immune to BA.5,” says Dr. Sander. Lessened immunity from BA.4 and BA.5 is even more pronounced. “Anyone who was infected with BA.1 is not immune to BA.5,” says Dr. Sander. The two clades not only have spike protein mutations shared by BA.2 but also additional spike protein mutations. According to the expert, it could well be that these strains will prevail because they are best able to avoid the immunity of the population.
Adapted vaccines feasible?
“Vaccines adapted to BA.1 were developed very early on and were also part of clinical research,” said Dr. Sander. The initial data indicate that additional antibody responses are being mobilized that may neutralize the new variants.
It was deduced from trials on monkeys that the available vaccines were so good that only small improvements were to be expected, said Dr. Sander.
Moderna’s adapted vaccine
The U.S. pharmaceutical company Moderna recently submitted the first results regarding its bivalent Omicron vaccine mRNA-1273.214, which is adapted to Omicron BA.1. Data from BioNTech are expected soon.
Moderna tested a booster that contains both the spike mRNA from the original vaccine and a new mRNA adapted to the Omicron variant BA.1. The experimental vaccine mRNA-1273.214 exhibited an eightfold increase in geometric mean neutralization titer against Omicron in study participants who were seronegative at the start, compared with the already-approved vaccine.
In its latest notice, Moderna did not publish any data on how effective the updated vaccine is against the virus variants BA.4 or BA.5. Data on clinical endpoints, such as hospitalization or mortality, are also not available.
Conservative epitopes
Should it be assumed that the development of vaccines will always lag the emergence of new subvariants? In this respect, Dr. Sander appears optimistic. “The immunological mechanism is clear, that various B cells and antibodies will be formed that are directed against conservative epitopes that have various variants. This is good news, since we do not want to protect against BA.1 now, just for BA.8 to emerge when the vaccine goes to market. We want to protect ourselves as broadly as possible, and it seems like it may be possible to do so with this vaccine.”
Double vaccination?
Dr. Sander anticipates that a fourth vaccination against COVID-19 will occur with the next wave of the coronavirus in September or October. He remarked that coupling it with the influenza vaccination should be considered.
The coronavirus pandemic has led to shifts in other seasonal waves of pathogens. In the summer, pediatric departments were unexpectedly inundated with children suffering from RSV infections. And while the flu season over the past 2 years has been almost absent, the influenza wave may occur significantly earlier than usual this year.
“In Australia, the influenza wave arrived much earlier this year than usual, which may of course also be fruitful for us,” said Dr. Sander. “Perhaps we will also get influenza as early as in September or October. I would then plead for vaccine centers to be allowed to vaccinate against both influenza and COVID-19 at the same time. Maybe then we will also have a reasonable influenza vaccination rate,” he added.
This article was translated from the Medscape German edition.
A version of this article first appeared on Medscape.com.
The fourth vaccination against COVID-19 is the subject of intense discussion. Immunity against new Omicron variants (currently BA.4 and BA.5) is getting weaker and weaker. Is another vaccination with the available vaccines worth it?
For Leif Erik Sander, MD, director of infectious diseases and pneumology at Charité University Medicine, Berlin, the latest data send a clear message. “The COVID-19 vaccination is still effective against Omicron. After three doses of the vaccine, it continues to prevent severe diseases, respiratory failures, and death,” he reported at the 62nd Congress of the German Pneumology and Respiratory Medicine Society in Leipzig.
The most recent data from the United Kingdom show that the vaccine’s effectiveness against Omicron decreases after just a few months, which speaks in favor of a fourth vaccination. “Omicron is a development that we did not anticipate occurring so early on,” said Dr. Sander.
In terms of phylogenetics, Omicron is far removed from the previous variants of concern. More than 30 mutations to the spike protein (the antigen that is vaccinated against) foster the loss of immunity.
Boosters broaden immunity
“The booster makes all the difference here,” emphasized Dr. Sander. Experiments at Charité Berlin show that after double vaccination, the vaccination sera from healthy young people no longer neutralizes Omicron.
“The third vaccination broadens the humoral immune response against the spike protein so that conserved epitopes that are unchanged, even in Omicron, are addressed, with the result that you have neutralization capacity again,” the infectious diseases specialist explained.
Continued protection
However, data from the United Kingdom on vaccine effectiveness show where the limit lies. Initially, after three doses, vaccine effectiveness against symptomatic disease after Omicron infection is very good. This effectiveness decreases significantly over the course of the next few months. “Lots of people experience an Omicron infection despite the booster,” said Mr. Sander.
Nonetheless, the high incidence of Omicron infections in the recent past has not overwhelmed the health care system. “This is because the vaccine’s effectiveness against severe diseases that require hospitalization and against respiratory failure is still good in the at-risk population over the age of 65, once they have had their three vaccinations,” said Dr. Sander. The data also show that there is good protection of over 90%, even against mortality.
Waning observed
It could be said that currently, vaccination even continues to work against Omicron, says Dr. Sander. It prevents severe disease, respiratory failure, and death. Nonetheless, after just 3 months, a slight waning of immune protection can be observed in all three endpoints.
Therefore, the question arises as to whether a fourth vaccination is worthwhile. In Israel, “Delta was successfully eradicated with the third vaccination,” and now they are trying this again for Omicron with a fourth vaccination, reported Dr. Sander.
Fourth vaccination protective
The first investigations show that protection against severe disease can be increased once more. “For the over-60s, protection is almost quadrupled through the fourth vaccination,” says Dr. Sander. “However, this is still plagued with a lot of uncertainty; it is still not known how stable it is.”
There is hope on the basis of results of an as yet non–peer-reviewed study from Sweden, which is currently available only as a preprint. That study shows that a fourth vaccination in a high-risk population of care-home residents and people older than 80 years can halve overall mortality. “If this can be confirmed and replicated, it must be recommended quite extensively for this high-risk group,” said Dr. Sander. The Standing Committee on Vaccination in Germany is currently recommending that high-risk groups be vaccinated against COVID-19 for the fourth time. To date, though, this has only been implemented halfheartedly.
Propensity for mutation
Omicron keeps developing. Following BA.1 and the more infectious subvariant BA.2, BA.4 and BA.5 are spreading in Germany. “To date, there is no evidence that vaccine protection against severe diseases has changed as a result of BA.2 emerging,” said Dr. Sander.
However, the loss of immunity against BA.4 and BA.5 is more strongly pronounced. “If you were infected with BA.1, you are not immune to BA.5,” says Dr. Sander. Lessened immunity from BA.4 and BA.5 is even more pronounced. “Anyone who was infected with BA.1 is not immune to BA.5,” says Dr. Sander. The two clades not only have spike protein mutations shared by BA.2 but also additional spike protein mutations. According to the expert, it could well be that these strains will prevail because they are best able to avoid the immunity of the population.
Adapted vaccines feasible?
“Vaccines adapted to BA.1 were developed very early on and were also part of clinical research,” said Dr. Sander. The initial data indicate that additional antibody responses are being mobilized that may neutralize the new variants.
It was deduced from trials on monkeys that the available vaccines were so good that only small improvements were to be expected, said Dr. Sander.
Moderna’s adapted vaccine
The U.S. pharmaceutical company Moderna recently submitted the first results regarding its bivalent Omicron vaccine mRNA-1273.214, which is adapted to Omicron BA.1. Data from BioNTech are expected soon.
Moderna tested a booster that contains both the spike mRNA from the original vaccine and a new mRNA adapted to the Omicron variant BA.1. The experimental vaccine mRNA-1273.214 exhibited an eightfold increase in geometric mean neutralization titer against Omicron in study participants who were seronegative at the start, compared with the already-approved vaccine.
In its latest notice, Moderna did not publish any data on how effective the updated vaccine is against the virus variants BA.4 or BA.5. Data on clinical endpoints, such as hospitalization or mortality, are also not available.
Conservative epitopes
Should it be assumed that the development of vaccines will always lag the emergence of new subvariants? In this respect, Dr. Sander appears optimistic. “The immunological mechanism is clear, that various B cells and antibodies will be formed that are directed against conservative epitopes that have various variants. This is good news, since we do not want to protect against BA.1 now, just for BA.8 to emerge when the vaccine goes to market. We want to protect ourselves as broadly as possible, and it seems like it may be possible to do so with this vaccine.”
Double vaccination?
Dr. Sander anticipates that a fourth vaccination against COVID-19 will occur with the next wave of the coronavirus in September or October. He remarked that coupling it with the influenza vaccination should be considered.
The coronavirus pandemic has led to shifts in other seasonal waves of pathogens. In the summer, pediatric departments were unexpectedly inundated with children suffering from RSV infections. And while the flu season over the past 2 years has been almost absent, the influenza wave may occur significantly earlier than usual this year.
“In Australia, the influenza wave arrived much earlier this year than usual, which may of course also be fruitful for us,” said Dr. Sander. “Perhaps we will also get influenza as early as in September or October. I would then plead for vaccine centers to be allowed to vaccinate against both influenza and COVID-19 at the same time. Maybe then we will also have a reasonable influenza vaccination rate,” he added.
This article was translated from the Medscape German edition.
A version of this article first appeared on Medscape.com.
CBT or hypnotherapy may help kids’ functional abdominal pain
Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.
“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
Signal perception disorder
“These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”
In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.
“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
Comparison of psychosocial therapies
The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.
Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.
Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
Rarer, milder pain
The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.
Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.
The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.
“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
Start with the pediatrician
Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.
Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
Education offers relief
For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.
“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.
“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.
A version of this article first appeared on Medscape.com.
Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.
“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
Signal perception disorder
“These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”
In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.
“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
Comparison of psychosocial therapies
The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.
Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.
Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
Rarer, milder pain
The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.
Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.
The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.
“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
Start with the pediatrician
Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.
Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
Education offers relief
For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.
“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.
“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.
A version of this article first appeared on Medscape.com.
Functional abdominal pain in childhood and adolescence is extremely stressful for patients and a therapeutic challenge for the physicians treating them. A meta-analysis of 33 randomized-controlled studies published in JAMA Pediatrics shows that cognitive-behavioral therapy or hypnotherapy promises the greatest therapy success.
“If children or adolescents complain about chronic abdominal pain and a detailed diagnostic does not reveal any somatic cause, this is referred to as functional abdominal pain,” Burkhard Rodeck, MD, general secretary of the German Society of Pediatrics and Adolescent Medicine in Berlin, told this news organization.
Signal perception disorder
“These patients are experiencing a signal perception disorder: normal body signals, such as a slight stomach rumble, are assigned to the pain category for them much more quickly than for other people,” said Dr. Rodeck. “The meta-analysis provides confirmation of this – functional abdominal pain is actually a biopsychosocial matter.”
In the standard therapy of functional abdominal pain, however, it is also possible to choose a medicinal approach. “Studies show that herbal preparations such as peppermint oil capsules have some efficacy, since they attenuate the strength of the signals being sent from the gastrointestinal tract to the brain, with the result that they are not perceived so quickly as pain. Probiotics can also potentially help,” added Dr. Rodeck.
“If this is unsuccessful, the child must be offered a psychologic/psychotherapeutic measure, usually cognitive-behavioral therapy.”
Comparison of psychosocial therapies
The meta-analysis was carried out by a research team at the University of Central Lancashire, Preston, United Kingdom. It included 2,657 children and adolescents between the ages of 7 and 17 years, of which two-thirds were girls.
Various psychosocial therapy approaches for functional abdominal pain, such as cognitive-behavioral therapy, educational assistance, hypnotherapy (directed at the digestive system), guided meditation with relaxation, yoga, or (visceral) osteopathy were investigated and compared in the studies – sometimes against each other and sometimes against no intervention.
Lead author Morris Gordon, MBChB, PhD, professor of evidence synthesis and systematic review at the University of Central Lancashire, and his colleagues reported that cognitive-behavioral therapy was 2.37-times more likely to result in therapy success than no intervention. To treat functional abdominal pain successfully in one child or adolescent, five children needed to be treated with cognitive-behavioral therapy.
Rarer, milder pain
The children and adolescents treated with cognitive-behavioral therapy also experienced less frequent and less severe abdominal pain than the children and adolescents who did not receive any intervention. The rate of side effect–related therapy discontinuations did not differ between the groups.
Hypnotherapy could also be associated with an improved outcome, compared with no intervention, added Dr. Gordon and his colleagues. Hypnotherapy was 2.86-times more likely to result in therapy success, and the number needed to treat was five.
The other therapeutic approaches investigated did not perform any better in the studies than no intervention. However, the authors noted that evidence of the effectiveness of cognitive-behavioral therapy and hypnotherapy is moderate or weak, especially owing to the high bias risk.
“The therapy for functional abdominal pain cannot be compared with the therapy for scarlet fever, for example, where penicillin is administered in the knowledge that recovery is guaranteed. There is evidence that cognitive-behavioral therapy and possibly also hypnotherapy may help, but this is not true for every patient,” said Dr. Rodeck.
Start with the pediatrician
Dr. Gordon and his co-authors suggested considering cognitive-behavioral therapy and hypnotherapy for the treatment of functional abdominal pain in children and adolescents. But they added that further randomized controlled studies are necessary to improve the quality of evidence and therefore the reliability of these results.
Children and adolescents with functional abdominal pain do not need to be sent directly to the psychologist for treatment, said Dr. Rodeck. The pediatric or adolescent medicine specialist can also administer the initial behavioral therapy measures. “Some patients manage with the behavioral therapy approaches we offer as pediatric and adolescent medicine specialists; others require professional support with psychologic expertise,” said Dr. Rodeck. Should outpatient treatment be unsuccessful, inpatient therapy in special psychosomatic clinics or wards remains an option.
Education offers relief
For many patients, being informed about the connections and mechanisms that play a role in functional abdominal pain can offer a lot of relief, said Dr. Rodeck. Offering coping strategies that can be used in the event of acute symptoms is also a part of this education.
“If patients have functional abdominal pain for which no organic cause can be found, this can lead to frustration, sadness, and despair. The problem can become even worse if they feel that they are not being taken seriously by the physician,” said Dr. Rodeck. These negative experiences can further exacerbate the pain perception disorder. The aim of behavioral therapy measures is therefore to interrupt and downregulate this vicious cycle.
“Constant investigations are not always helpful for patients with functional abdominal pain. Time must be taken with these patients to talk and explore the options. They have definite abdominal pain, they are not imagining it. They must be taken seriously,” he emphasized.
A version of this article first appeared on Medscape.com.
Reducing night-time checks is safe and helps patients sleep
Routine checks of vital signs during the night often prevent hospitalized patients from getting sufficient recuperative sleep. But patients who are judged to be clinically stable by an algorithm that uses real-time data can be safely spared these checks, according to a recent study published in JAMA Internal Medicine.
In their study,
“Sleep is crucial to health,” writes Hyung J. Cho, MD, from the New York University Grossman School of Medicine, in an accompanying editorial. “Ironically, hospitals, where people go to recover from illness, are among the most difficult places to sleep.”
Noise from the surrounding area, night-time examinations, multibed rooms, an unfamiliar environment, early morning blood sample collections, and frequent vital sign checks often prevent patients from sleeping through the night.
The goal of the study was to see if the elimination of one of these disrupting factors – the frequent checks of vital signs – would improve sleep and lead to a reduction in delirium, the primary endpoint.
To do this, the researchers incorporated a predictive algorithm they developed “to identify patients who are at low risk for abnormal night-time vital signs” into the hospitals electronic health records system. Attending physicians received a notification, based on real-time patient data, if it was predicted with a high degree of probability that a patient’s night-time vital signs would be within the normal range. Each physician was free to decide whether they would forgo night-time checks of the vital signs or whether they would turn off the notifications for a specific period.
The randomized clinical trial was conducted at a tertiary care academic teaching hospital from March to November 2019. Half the 1,930 patients were randomized to the algorithm group and half to standard care. None of the patients were receiving intensive care.
Number of night-time checks successfully reduced
The mean number of night-time checks was significantly lower in the algorithm group than in the standard-care group (0.97 vs. 1.41; P < .001).
The reduction in night-time checks had no effect on patient safety. There was no increase in transfers to the intensive care unit in the algorithm or standard-care groups (5% vs 5%; P = .92), and no difference between the number of heart alarms (0.2% vs. 0.9%; P = .07).
However, the reduction also had no effect on the incidence of episodes of delirium in the algorithm or standard-care groups (11% vs. 13%; P = .32).
“The reduction in vital signs checking, although statistically significant, was relatively small,” Dr. Cho explains. But the primary endpoint might have been different had the adherence to intervention been better, he notes.
In fact, the analysis confirmed that changes to routine daily practice in a hospital are not always easy to implement. In 35% of cases, the patients’ vital signs were checked at night, despite the physician’s order to the contrary.
“Busy patient-care assistants and nurses may check vital signs out of habit without noticing that the order has changed for some of the patients,” Dr. Najafi and his coauthors write. Many hospitals are used to thinking that regular measurements of the vital signs are part of good practice.
Include nursing staff
Future projects should use an interdisciplinary approach that includes nursing staff, Dr. Cho recommends. More user-friendly displays and optimized alerts in the electronic patient records could also encourage better implementation of the orders.
Less frequent checks of the vital signs would be welcomed by frontline staff because it would lighten their already heavy workload, he adds.
Although the study didn’t meet its primary endpoint, patients subjected to fewer night-time checks because of the algorithm were able to get a good night’s sleep. Other aspects of hospital care that are based on the patient’s stability, such as cardiac monitoring, could also potentially benefit from this type of intervention, Dr. Najafi and his colleagues suggest.
A version of this article first appeared on Medscape.com.
Routine checks of vital signs during the night often prevent hospitalized patients from getting sufficient recuperative sleep. But patients who are judged to be clinically stable by an algorithm that uses real-time data can be safely spared these checks, according to a recent study published in JAMA Internal Medicine.
In their study,
“Sleep is crucial to health,” writes Hyung J. Cho, MD, from the New York University Grossman School of Medicine, in an accompanying editorial. “Ironically, hospitals, where people go to recover from illness, are among the most difficult places to sleep.”
Noise from the surrounding area, night-time examinations, multibed rooms, an unfamiliar environment, early morning blood sample collections, and frequent vital sign checks often prevent patients from sleeping through the night.
The goal of the study was to see if the elimination of one of these disrupting factors – the frequent checks of vital signs – would improve sleep and lead to a reduction in delirium, the primary endpoint.
To do this, the researchers incorporated a predictive algorithm they developed “to identify patients who are at low risk for abnormal night-time vital signs” into the hospitals electronic health records system. Attending physicians received a notification, based on real-time patient data, if it was predicted with a high degree of probability that a patient’s night-time vital signs would be within the normal range. Each physician was free to decide whether they would forgo night-time checks of the vital signs or whether they would turn off the notifications for a specific period.
The randomized clinical trial was conducted at a tertiary care academic teaching hospital from March to November 2019. Half the 1,930 patients were randomized to the algorithm group and half to standard care. None of the patients were receiving intensive care.
Number of night-time checks successfully reduced
The mean number of night-time checks was significantly lower in the algorithm group than in the standard-care group (0.97 vs. 1.41; P < .001).
The reduction in night-time checks had no effect on patient safety. There was no increase in transfers to the intensive care unit in the algorithm or standard-care groups (5% vs 5%; P = .92), and no difference between the number of heart alarms (0.2% vs. 0.9%; P = .07).
However, the reduction also had no effect on the incidence of episodes of delirium in the algorithm or standard-care groups (11% vs. 13%; P = .32).
“The reduction in vital signs checking, although statistically significant, was relatively small,” Dr. Cho explains. But the primary endpoint might have been different had the adherence to intervention been better, he notes.
In fact, the analysis confirmed that changes to routine daily practice in a hospital are not always easy to implement. In 35% of cases, the patients’ vital signs were checked at night, despite the physician’s order to the contrary.
“Busy patient-care assistants and nurses may check vital signs out of habit without noticing that the order has changed for some of the patients,” Dr. Najafi and his coauthors write. Many hospitals are used to thinking that regular measurements of the vital signs are part of good practice.
Include nursing staff
Future projects should use an interdisciplinary approach that includes nursing staff, Dr. Cho recommends. More user-friendly displays and optimized alerts in the electronic patient records could also encourage better implementation of the orders.
Less frequent checks of the vital signs would be welcomed by frontline staff because it would lighten their already heavy workload, he adds.
Although the study didn’t meet its primary endpoint, patients subjected to fewer night-time checks because of the algorithm were able to get a good night’s sleep. Other aspects of hospital care that are based on the patient’s stability, such as cardiac monitoring, could also potentially benefit from this type of intervention, Dr. Najafi and his colleagues suggest.
A version of this article first appeared on Medscape.com.
Routine checks of vital signs during the night often prevent hospitalized patients from getting sufficient recuperative sleep. But patients who are judged to be clinically stable by an algorithm that uses real-time data can be safely spared these checks, according to a recent study published in JAMA Internal Medicine.
In their study,
“Sleep is crucial to health,” writes Hyung J. Cho, MD, from the New York University Grossman School of Medicine, in an accompanying editorial. “Ironically, hospitals, where people go to recover from illness, are among the most difficult places to sleep.”
Noise from the surrounding area, night-time examinations, multibed rooms, an unfamiliar environment, early morning blood sample collections, and frequent vital sign checks often prevent patients from sleeping through the night.
The goal of the study was to see if the elimination of one of these disrupting factors – the frequent checks of vital signs – would improve sleep and lead to a reduction in delirium, the primary endpoint.
To do this, the researchers incorporated a predictive algorithm they developed “to identify patients who are at low risk for abnormal night-time vital signs” into the hospitals electronic health records system. Attending physicians received a notification, based on real-time patient data, if it was predicted with a high degree of probability that a patient’s night-time vital signs would be within the normal range. Each physician was free to decide whether they would forgo night-time checks of the vital signs or whether they would turn off the notifications for a specific period.
The randomized clinical trial was conducted at a tertiary care academic teaching hospital from March to November 2019. Half the 1,930 patients were randomized to the algorithm group and half to standard care. None of the patients were receiving intensive care.
Number of night-time checks successfully reduced
The mean number of night-time checks was significantly lower in the algorithm group than in the standard-care group (0.97 vs. 1.41; P < .001).
The reduction in night-time checks had no effect on patient safety. There was no increase in transfers to the intensive care unit in the algorithm or standard-care groups (5% vs 5%; P = .92), and no difference between the number of heart alarms (0.2% vs. 0.9%; P = .07).
However, the reduction also had no effect on the incidence of episodes of delirium in the algorithm or standard-care groups (11% vs. 13%; P = .32).
“The reduction in vital signs checking, although statistically significant, was relatively small,” Dr. Cho explains. But the primary endpoint might have been different had the adherence to intervention been better, he notes.
In fact, the analysis confirmed that changes to routine daily practice in a hospital are not always easy to implement. In 35% of cases, the patients’ vital signs were checked at night, despite the physician’s order to the contrary.
“Busy patient-care assistants and nurses may check vital signs out of habit without noticing that the order has changed for some of the patients,” Dr. Najafi and his coauthors write. Many hospitals are used to thinking that regular measurements of the vital signs are part of good practice.
Include nursing staff
Future projects should use an interdisciplinary approach that includes nursing staff, Dr. Cho recommends. More user-friendly displays and optimized alerts in the electronic patient records could also encourage better implementation of the orders.
Less frequent checks of the vital signs would be welcomed by frontline staff because it would lighten their already heavy workload, he adds.
Although the study didn’t meet its primary endpoint, patients subjected to fewer night-time checks because of the algorithm were able to get a good night’s sleep. Other aspects of hospital care that are based on the patient’s stability, such as cardiac monitoring, could also potentially benefit from this type of intervention, Dr. Najafi and his colleagues suggest.
A version of this article first appeared on Medscape.com.