Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

Anxiety symptoms in children are common, ranging from a toddler’s fear of the dark to an adolescent worrying about a major exam. Anxiety disorders, symptoms that are persistent and impact functioning, are the most common psychiatric illnesses of childhood. The good news is that, if they are detected early and treated appropriately, they are curable. Unfortunately, they are often silent, or present with misleading symptoms. Screening for anxiety disorders, especially in the presence of the most common presenting concerns, can illuminate the true nature of a child’s challenge and point the way forward. In this month’s article, we will provide details on the prevalence of anxiety disorders in children, how they typically present, and how best to screen for them. We will offer some strategies for speaking about them with your patients and their parents, as well as introduce some of the strategies that can improve mild to moderate anxiety disorders. We will follow up with another piece on the evidence-based treatments for these common disorders, how to find appropriate referrals, and what you can do in your office to get treatment started.

Anxiety disorders: Common and treatable

Anxiety disorders – including separation anxiety disorder, social phobia, simple phobias, generalized anxiety disorder, panic disorder, and PTSD – affect between 15% and 20% of children before the age of 18, with some recent estimates as high as 31.9% of youth being affected. Indeed, the mean age of onset for most anxiety disorders (excluding panic disorder and PTSD) is between 5 and 9 years of age. Despite being so common, many anxiety disorders in childhood are never properly diagnosed, and most (as many as 80%) do not receive treatment from a mental health professional. With early diagnosis and evidence-based treatment, most anxiety disorders can be “cured” and no longer impair functioning. Untreated, anxiety disorders usually have a chronic course, causing significant behavioral problems and disruption of a child’s critical social, emotional, and identity development and their academic function. Untreated, they are frequently complicated in adolescence by mood, substance use, and eating disorders. With the passage of time, developmental consequences and comorbid illnesses, a curable childhood anxiety disorder can become a complex and entrenched psychiatric syndrome in young adulthood.

One of the reasons these illnesses frequently go unrecognized is that states of fearful distress, such as separation anxiety or social anxiety, are developmentally normal at different stages of childhood, and it can be difficult to discriminate between normal and pathological anxiety. Anxiety itself is an “internalizing” symptom, and is invisible except for the behaviors that can accompany it. Some behaviors suggest anxiety, such as fearful expressions, clinginess, excessive need for reassurance, or avoidance. But anxiety can also lead to obstinate refusal to do certain things. It might lead to explosive tantrums when a child is pushed to do something that makes them intensely anxious. It can lead to irritability and moody tantrums for a child exhausted after a long school day spent managing high levels of anxiety by themselves. Anxious children often appear inattentive in school. Anxiety disorders frequently disrupt restful sleep, leading to children who are irritable and moody as well as inattentive. These children may present to the pediatrician with frustrated parents concerned that they are oppositional or explosive, or because their teachers are concerned about ADHD, when the culprit is actually anxiety.

While anxiety is uncomfortable, these children are unlikely to experience their anxiety as unusual and foreign, like a sudden toothache. Instead, it feels to them like they are fearful for good reason, responding appropriately to something real. These children are more likely to respond to a novel or uncertain situation with worry rather than curiosity, and to a new challenge as a threat. For children who are managing their anxiety more internally, their parents are often unaware of their degree of distress. Indeed, these children are often careful, thoughtful, and attentive to detail. Parents and teachers may think they are doing wonderfully. They are typically very sensitive to physical discomforts, which are heightened by an anxious state. These are likely to present to the pediatrician’s office with parents very worried about a cluster of vague physical complaints (stomach ache, headache, “just not feeling good”), which coincides with a change, challenge, or anxious stimulus. In this situation, the parents may dismiss the possibility of anxiety, and the child may not even be aware of it. But it will get worse if they are pushed to bear the source of anxiety (going to school, sports practice, etc.).
 

Anxiety screening and treatment

When a child presents for a sick visit with vague symptoms, or a negative workup for specific ones, you should screen them for an anxiety disorder. When they present with concerns about inattention, insomnia, moodiness, obstinacy, and even explosive behaviors, you should screen them for an anxiety disorder. This is especially true if they are prepubertal, when anxiety disorders are far more common than mood disorders. But you should consider anxiety disorders alongside mood disorders in adolescents presenting with these complaints. While parents may be unaware of the presence of anxiety in their child, explain to them that anxiety disorders are very common and treatable in childhood to help them understand the value of screening. Asking children directly about their internal experience can also be helpful. Avoid asking about “anxiety,” instead asking if they ever worry about specific things, such as “talking to kids you don’t know at recess,” “being alone at home,” “getting robbed or kidnapped,” or “something bad happening to your parents.” Just asking helps children pay attention to their thoughts and feelings, and is a powerful screening instrument.

There are also real screening instruments that you might use routinely for sick visits in prepubertal children or when anxiety should be in the differential. These instruments can be prone to recall bias, but generally make it easier for (anxious) children to accurately describe their internal experience. An instrument like the GAD7 is brief, free, and sensitive, but not very specific. If it is positive, you can then offer a longer screen such as the SCARED, also free, which indicates likely diagnoses such as generalized anxiety disorder, separation anxiety disorder, panic disorder, and social phobia. There is a parent version and a self-report, and it is validated for youths 8-18 years old and takes approximately 20 minutes to complete and score.

A positive screen should lead to a more nuanced conversation with your patient and their parents about their anxiety symptoms. You may feel comfortable doing a more extensive interview to make the likely diagnosis or may prefer to refer to a psychiatrist or psychologist to assist with diagnosis and treatment recommendations. In either case, you can offer your patient and their parents meaningful reassurance that the intense discomfort of their anxiety will get better with effective treatment. In this visit, you can get treatment started by identifying what parents and their children can do right away to begin addressing anxiety symptoms. Offer strategies to protect and promote restful sleep and daily vigorous exercise, both of which can directly improve mild to moderate anxiety symptoms. Suggest to parents that they should help their children to notice what they are feeling, rather than rushing in to remove a source of anxiety. These measures can help their child to identify what is a thought, a feeling, a physical sensation, or a fact. They can offer support and validation around how uncomfortable these feelings are, but just being curious will reassure their child that they will be able to manage and master this feeling. This “practice” is akin to what their child will do in most effective treatments, and will have the added benefit of helping them to build skills that all children need to manage the challenges and worries that are a normal, but difficult part of growing up and of adult life. Finally, you can tell them that anxious temperaments come with advantages also, such as great powers of observation, attention to detail, and thoroughness, high levels of empathy, drive, and tenacity. By learning to manage anxiety early, these children can grow up to be engaged, resilient, successful, and satisfied adults.

Once identified, the range of effective treatments available include cognitive-behavioral therapy, graduated exposure, mindfulness/relaxation techniques, and medication, and we will discuss these in our next article.

Dr. Swick is physician in chief at Ohana, Center for Child and Adolescent Behavioral Health, Community Hospital of the Monterey (Calif.) Peninsula. Dr. Jellinek is professor emeritus of psychiatry and pediatrics, Harvard Medical School, Boston. Email them at pdnews@mdedge.com.

Reference

Beesdo K et al. Anxiety and anxiety disorders in children and adolescents: developmental issues and implications for DSM-V. Psychiatr Clin North Am. 2009 Sep. doi: 10.1016/j.psc.2009.06.002.

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

TOPLINE:

Adults with high-risk serrated polyps (with or without high-risk adenomas) have a high risk for metachronous colorectal cancer (CRC) within a median of 3 years after the baseline colonoscopy for a positive fecal immunochemical test (FIT) screen, a study suggests.

,

METHODOLOGY:

• Investigators conducted a retrospective analysis of 253,833 colonoscopies performed after FIT-positive screens in a Dutch CRC screening program.
• A Cox regression analysis assessed the association between the findings at baseline colonoscopy and metachronous CRC risk.
• Investigators categorized patients into subgroups based on removed polyp subtypes and used groups without polyps as a reference.
• High-risk subgroups included those with high-risk serrated polyps, which were defined as a serrated polyp of at least 10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, which were defined as an adenoma of at least 10 mm or containing high-grade dysplasia.

TAKEAWAY:

• Over a median follow-up of 36 months, 504 metachronous CRCs were identified.
• Individuals with high-risk serrated polyps without co-occurring high-risk adenomas had an increased risk for metachronous CRC (hazard ratio, 1.70).
• The highest risk was seen in individuals with both high-risk serrated polyps and high-risk adenomas (HR, 2.0), as well as those with villous adenomas (HR, 2.07).
• Individuals with only high-risk adenomas did not show a significantly increased risk for metachronous CRC (HR, 1.22).

IN PRACTICE:

“Our results suggest that individuals with high-risk serrated polyps might comprise the higher CRC risk in the first years after colonoscopy. Results of this study could contribute to establish more restrictive polyp surveillance guidelines in a quality-assured setting,” the authors wrote.

SOURCE:

The study was led by David E. F. W. M. van Toledo, MD, department of gastroenterology and hepatology, Amsterdam University Medical Centers. It was published online July 5, 2023, in eClinicalMedicine. The study received no funding.

LIMITATIONS:

The relatively short median follow-up time of 3 years may limit the assessment of long-term metachronous CRC risk. The study population consisted of FIT-positive individuals, which may introduce selection bias. The incidence of metachronous CRC in the study was lower compared with other studies, potentially affecting the risk estimates. The limited number of cases in some subgroups may result in unreliable risk estimations.

DISCLOSURES:

Dr. van Toledo declared no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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

New research supports the use of liquid biopsy as an adjunct biomarker for the diagnosis and surveillance of human papillomavirus (HPV)–associated oropharyngeal cancer.

In a retrospective observational cohort study, a commercially available blood test used to evaluate tumor tissue–modified viral-HPV DNA demonstrated 100% specificity for both diagnosis of oropharyngeal cancer and surveillance for recurrence. Sensitivity was 91.5% for correctly identifying patients who have the disease and 88.4% for surveillance.

“A positive result appeared to confirm the presence of disease, [but] approximately 1 in 10 negative results in patients with pathologically confirmed HPV-associated oropharyngeal squamous cell carcinoma were falsely negative,” lead investigator Rocco Ferrandino, MD, with Mount Sinai, New York, said in an interview.

“Therefore, further workup should still be pursued when clinical suspicion for HPV-associated oropharynx cancer is high,” Dr. Ferrandino said.

The study was published online, in JAMA Otolaryngology–Head and Neck Surgery, to coincide with presentation at the annual meeting of the American Head and Neck Society in Montreal.
 

‘Remarkable promise’

The diagnosis of HPV-associated oropharyngeal cancer currently relies on a tissue-based biopsy of the primary site or a regional lymph node; however, there has been growing interest in the potential of liquid biopsy for diagnosis and surveillance.

The commercially available assay that was evaluated in the study uses a distinct method to identify and quantify a tumor-associated or tumor-modified pattern of DNA fragments that significantly increases the specificity for identifying an HPV-associated malignant tumor. However, evaluation of the assay has been limited to small cohort studies and clinical trials.

In the current study, Dr. Ferrandino and colleagues evaluated the performance of the assay used during routine clinical practice at their high-volume institution over a period of nearly 3 years.

The study included 163 patients in the diagnostic cohort and 290 in the surveillance cohort. In the diagnostic cohort, 152 had HPV-associated oropharyngeal cancer, and 11 had HPV-negative oropharyngeal cancer. The sensitivity of the assay in pretreatment diagnosis was 91.5% (139 of 152 tests), and the specificity was 100% (11 of 11 tests).

In the surveillance cohort of 290 patients, 591 tests were evaluated. A total of 23 patients developed pathologically confirmed recurrences over a median follow-up of 40.5 months. The assay demonstrated sensitivity of 88.4% (38 of 43 tests) and specificity of 100% (548 of 548 tests) in detecting recurrences.

The median lead time from positive test to pathologic confirmation was 47 days.

“The lead time provided by positive assay results may allow a window of opportunity for salvage treatment or for the application of adjuvant systemic therapy,” Dr. Ferrandino and colleagues explain.

“While these results are exciting and may support adjunctive use of circulating tumor DNA testing for diagnosis and surveillance, we really need more prospective and multicenter studies to validate these findings,” Dr. Ferrandino said in an interview.

In an accompanying commentary, Miriam Lango, MD, department of head and neck surgery, the University of Texas MD Anderson Cancer Center, Houston, said she agrees that a prospective clinical validation study is needed.

“Nevertheless, the use of this technology shows remarkable promise to transform the ability to identify and follow patients with HPV-related disease. Testing is likely to be increasingly used in routine clinical care, as it is commercially available,” Dr. Lango writes.

Still, she noted, “It is incumbent on us to establish evidence for strong and detailed surveillance guidelines to share among the cancer community.”

The study had no specific funding. Dr. Ferrandino and Dr. Lango have disclosed no relevant financial relationships.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Kathy Blackwell is not going to allow a couple of aching joints stop her from living her best life.
 

The 73-year-old resident of Simi Valley, Calif., a bedroom community about 30 miles northwest of downtown Los Angeles, organizes regular activities for her group of seniors. The 20- to 30-member-strong band of seasoned citizens, mostly women, keep active. Over the coming weeks, they plan to catch the Beach Boys at the historic Hollywood Bowl and take a cruise to Alaska. 

The busy schedule is why Ms. Blackwell intends to delay her second hip replacement surgery, opting instead for a cortisone shot in hopes of easing the pain enough to enjoy the upcoming excursions.

Not that she is shy about joint replacement. If her orthopedic surgeon offered a frequent customer punch card like the ones you get at the local coffee shop, hers would be nearly full. Ms. Blackwell’s knees and a hip have been replaced, and her other hip will be, too, once her calendar clears up.

“If you go on enough with chronic pain where there’s no relief, you get cranky,” Ms. Blackwell said.
 

More than 1 million new knees, hips

Joint replacements are getting more common, with about 790,000 total knee replacements and more than 450,000 hip replacements performed annually in the United States, according to the American College of Rheumatology.

Experts agree age is not a factor when considering candidates for joint replacement. Rafael Sierra, MD, of the Mayo Clinic, Rochester, Minn., said he’s done hip replacements on patients as young as 12 and as old as 102. Orthopedic surgeon John Wang, MD, of the Hospital for Special Surgery, New York, has performed a total knee arthroscopy on a patient in their mid-90s. At 73, Ms. Blackwell is on the older side of the average age of 66 for a hip replacement.

“A lot of research and studies have shown that no matter what the age ranges, people end up doing great,” Dr. Wang said.

More importantly than age, older patients should be prepared for postsurgery therapy and treatment. For younger patients, the biggest drawback is outliving the estimated 25-year life span of a joint replacement. Complications are rare and occur in about 2% of procedures. These include infection, dislocation of the joint, and blood clots; other health issues you also have are not a factor.

Considering Ms. Blackwell’s hard time with her first knee replacement, it’s no small wonder that she ever set foot in a surgeon’s office again.

After putting it off for 7 years, Ms. Blackwell finally agreed to her doctor’s advice to replace her left knee in 2017 to relieve what she described as a “grinding,” chronic, bone-on-bone pain.

“It got to the point where there were no alternatives,” she said.

But her first orthopedic surgeon did a “lousy job,” leaving her with a gaping, festering wound that resulted in sepsis and required wound vacuum therapy to close the lesion. She eventually found another surgeon who removed and cleaned up her artificial knee before replacing the prosthesis. Luckily, the sepsis didn’t spread, and eight surgeries later, she was in the clear.

Ms. Blackwell’s second knee replacement in 2018 was a textbook surgery, as was a hip replacement in late 2019 .

“Your whole attitude changes,” she said.
 

What generalists should know

Orthopedic surgeons recommend that primary care doctors ask two things when weighing joint replacements: Have they exhausted nonsurgical treatments, and is the pain intolerable? They also advise avoiding narcotics to treat the symptoms.

The top issue to consider for a primary care doctor when weighing whether their patient may be a candidate for joint replacement is if the pain and the imaging are bad enough to warrant surgery.

“You don’t want to do it too soon,” Dr. Sierra said.

Dr. Sierra likes to tell the story of the golfer whose knee stiffens after playing 18 holes. To those patients, he recommends dialing back the activity; in this case, using a cart or playing only nine holes.

Dr. Wang agrees, asking if the pain is “lifestyle altering” and if the patient was unresponsive to nonsurgical treatments such as over-the-counter medications, anti-inflammatory medication and shots, home exercises or physical therapy, wearing a brace or sleeve, or simply changing their activity.

And no addictive pain pills to treat arthritis that can lead to other serious issues.

“This is not going to heal itself,” Dr. Wang said. “It’s not going to improve on its own. So, we don’t want to throw narcotics at it just to cover it up.”

Karen Smith, MD, has been a family doctor in rural North Carolina for more than 30 years. When she sees patients complaining about their joints, she first looks at function and pain. From there, she explores why they’re having discomfort. For example, is the problem an ergonomic issue at work or the result of carrying a lot of body weight?

“We look at those areas to determine what can be modified,” she said. “All of that’s done even before we get to having the orthopedic involvement.”

Dr. Smith said she also considers things beyond basic medicine: What is the patient’s mental status and tolerance for pain? Do they have a support system at home for post-operative care? And can they afford to miss work?

“We look at all of those factors together because that is going to determine the outcome that we’re hoping to achieve,” Dr. Smith said.
 

Great expectations

A recent study shows that older patients respond better to knee replacements than younger patients, particularly with pain relief and quality of life. The reason for this is believed to boil down to expectations. Whereas a younger person may want to return to the racquetball court and perform like they used to, older patients may just wish to walk down the hall without discomfort.

“It’s possible that these under 55-age-old patients may just take a little longer to heal to be satisfied,” Dr. Wang said. “We really can’t speak to why this is happening, but it’s possible that the younger patients are more active, and they expect more out of their knee.”

Jeevan Sall, MD, is a primary care sports medicine doctor with Providence Mission Heritage Medical Group in Laguna Niguel, Calif. He first discusses conservative management for patients struggling with arthritis in their joints. These measures include rehabilitation exercises, braces, shoe inserts, medication, and weight loss efforts. If these steps don’t improve a patient’s pain or lifestyle, surgery is on the table. Managing expectations is a significant factor.

“Is the patient mentally ready for surgery?” Dr. Sall said. “This includes what they hope to achieve with surgery as well as the risk and benefits of the procedure.”

Ms. Blackwell’s hip and knee pain came simply from a life well lived, with no marathon running or life-changing accident to speak of. She worked as a housewife raising her two children and owned an elevator company with her late husband, Robert Blackwell.

Yes, the elevator construction business has jokes.

“We have our ups and downs,” Ms. Blackwell said.

And with her new joints, so does she.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

Micronized oral progesterone might decrease night sweats and improve sleep in perimenopausal women, according to new research.

In a randomized, placebo-controlled trial of about 180 women with vasomotor symptoms (VMS), women who received progesterone perceived a significantly greater decrease in night sweats (P = .023) and improved sleep quality (P = .005), compared with controls. VMS score did not differ significantly by treatment group, however.

“Women who have menstruated within the last year, who are waking twice or more times a week with night sweats and bothered by sleep disturbances would benefit from taking oral micronized progesterone 300 mg at bedtime,” principal investigator Jerilynn C. Prior, MD, professor of endocrinology at the University of British Columbia in Vancouver, British Columbia, Canada, said in an interview.

The study was published online in Scientific Reports.
 

A neglected group?

The best management for symptoms in perimenopause is an often-neglected topic of research, said Dr. Prior. Yet perimenopause is often associated with significant symptoms for women, including heavy menstrual bleeding, sore breasts, mood swings, night sweats, and insomnia – all when many women are at the peak of their careers.

Dr. Prior herself had a difficult perimenopause. “I began having cyclic night sweats, clustered around flow, when I was still having regular menstrual cycles, plus breast tenderness and sleep problems,” she said. “I knew from my research and my own experience that my estrogen levels were very high. Higher estrogen levels are not suppressible by exogenous estrogen, so it made no sense to me to ask my family doctor for a prescription for estrogen – or hormone replacement therapy, as it was then called. However, medroxyprogesterone acetate had been reported to be effective for menopausal hot flushes. I tried it, and it helped my night sweats and hot flushes but not my sleep. When oral micronized progesterone became available, I switched to that.”

In the current study, which was performed at the UBC Centre for Menstrual Cycle and Ovulation Research, the investigators studied 189 community-dwelling women from across Canada who were aged 35-58 years, had menstruated in the past year, and were bothered by daytime flushes or night sweats at least twice per week.

Participants were randomly assigned to receive either 300 mg of oral micronized progesterone or placebo at bedtime for 3 months. They recorded VMS number and intensity while awake and asleep each day. Some women participated remotely by web conference, telephone, or email. The experimental medicine was delivered to these participants by courier. The primary outcome was VMS score during the 3rd month.

Most (87%) participants were White, and about 57% had a college degree. The population’s average body mass index was 26.7, and 66.7% of participants were in late perimenopause.

The mean baseline VMS score among the women was 12.2. The average frequency of VMS per 24-hour day was 4.9. Average VMS intensity was 2.3 on a scale of 0-4. VMS scores decreased over time in both treatment groups.

At month 3, the VMS score was 5.5 in the progesterone group and 7.1 in the placebo group. The difference between groups was not statistically significant.

Compared with controls, however, women in the progesterone group perceived a significantly greater decrease in night sweats and improved sleep quality. Progesterone also was associated with significantly decreased perception of physical and emotional interference with their daily activities, compared with placebo (P = .017). Moreover, progesterone did not increase depression.

There were no serious adverse events.

“I hope that when women who look young and are still menstruating in their late 30s to early 50s go to the doctor and ask for help with night sweats and sleep problems, they will be told about this trial and offered progesterone therapy. I also hope they won’t be told, ‘You are too young,’ or ‘You are not in menopause,’ with the inference that the issue is all in their minds,” said Dr. Prior.
 

Useful dosing information

Mitchell S. Kramer, MD, chair of obstetrics and gynecology at Huntington (N.Y.) Hospital Northwell Health, said in a comment that “progesterone has been used for quite a while. I’ve been treating menopausal and perimenopausal hormonal disturbances and VMS for many years, and progesterone has been a real staple of treatment for these symptoms, especially in perimenopausal patients who are not good candidates for estrogen or who won’t accept treatment with estrogen. It’s actually nice to see a study that addresses this issue in a randomized controlled fashion and that confirms the efficacy of progesterone.”

The most helpful aspect of the study is the dosing information, Dr. Kramer added. “They recommend a 300-mg dose of oral micronized progesterone, which is much higher than I normally use. I may start to prescribe the higher dose and perhaps get a better or more complete response. There were no adverse events reported in this study, so the higher dose was enlightening to me,” he said.

Perimenopause is a time that is challenging to manage, said Michelle Jacobson, MD, of the department of obstetrics and gynecology at the University of Toronto, and obstetrician-gynecologist at Women’s College and Mount Sinai Hospitals in Toronto.

“There are so many nuances to the management. Women are suffering oftentimes from classic menopausal symptoms. There are fluctuating levels of estrogen, sometimes high. Sometimes there are complications of bleeding. There is the potential need for contraception because they are still menstruating,” she said in an interview.

“It’s important to specifically study this group of women with their own unique needs. Dr. Prior is a longtime proponent of using progesterone therapy, and kudos to her for doing this study in perimenopausal women, which is a group that is probably underrepresented in the menopause management literature,” she said.

Dr. Prior and Dr. Kramer reported no relevant financial relationships. Dr. Jacobson reported financial relationships with Astellas, AbbVie, Bayer, BioSyent, Duchesnay, Eisai, Lupin, Organon, Pfizer, and Searchlight.

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

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The history and findings in this case are suggestive of late-onset familial AD (onset after age 65 years).

AD is a common neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. In 2020, 5.8 million Americans were living with AD. By 2050, this number is projected to increase to 13.9 million people, or almost 3.3% of the US population. Globally, 152 million people are projected to have AD and other dementias by 2050. The worldwide increase in incidence and prevalence of AD is at least partially explained by an aging population and increased life expectancy. 

The cause of AD remains unclear, but there is substantial evidence that AD is a highly heritable disorder. Familial AD is characterized by having more than one member in more than one generation with AD. The autosomal-dominant form of AD is linked to mutations in three genes: AAP on chromosome 21, PSEN1 on chromosome 14, and PSEN2 on chromosome 1. APP mutations may cause increased generation and aggregation of beta-amyloid peptide, whereas PSEN1 and PSEN2 mutations result in aggregation of beta-amyloid by interfering with the processing of gamma-secretase.

APOE is another genetic marker that increases the risk for AD. Isoform e4 of the APOE gene (located on chromosome 19) has been associated with more sporadic and familial forms of AD that present after age 65 years. Approximately 50% of individuals carrying one APOEe4 develop AD, and 90% of individuals who have two alleles develop AD. Variants in the gene for the sortilin receptor, SORT1, have also been found in familial and sporadic forms of AD.

The cognitive and behavioral impairment associated with AD significantly affects a patient's social and occupational functioning. Insidiously progressive memory loss is a characteristic symptoms seen in patients presenting with AD. As the disease advances over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. A slow progression of behavioral changes may also occur in individuals with AD.

Clinical criteria for the diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are often used to diagnose patients. In addition, biomarker evidence may help to increase the diagnostic certainty. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid-beta for AD.

Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD because it allows for accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT can be used when MRI is not available or is contraindicated, such as in a patient with a pacemaker. PET is another noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, which marked a significant achievement to improve AD diagnosis. 

At present, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical treatments for AD. Antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid-beta–directed antibody that was approved in 2021, and lecanemab, another amyloid-beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, can be treated with psychotropic agents. Behavioral interventions including patient-centered approaches and caregiver training can also be helpful for managing the cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise may also play a role in delaying AD progression and possibly conferring a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
 

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

The COVID-19 vaccines have been a game changer for millions of people worldwide in preventing death or disability from the virus. Research suggests that they offer significant protection against long COVID.

Studies have consistently found that these vaccines prevent the new onset of long COVID as well as flare-ups for people who already have the condition.

False and unfounded claims made by some antivaccine groups that the vaccines themselves may cause long COVID persist and serve as barriers to vaccination.

To help separate the facts from falsehoods, here’s a checklist for doctors on what scientific studies have determined about vaccination and long COVID.
 

What the research shows

Doctors who work in long COVID clinics have for years suspected that vaccination may help protect against the development of long COVID, noted Lawrence Purpura, MD, MPH, an infectious disease specialist at New York–Presbyterian/Columbia University Irving Medical Center, who treats patients with long COVID in his clinic.

Over the past year, several large, well-conducted studies have borne out that theory, including the following studies:

• In the RECOVER study, published in May in the journal Nature Communications, researchers examined the electronic health records of more than 5 million people who had been diagnosed with COVID and found that vaccination reduced the risk that they would develop long COVID. Although the researchers didn’t compare the effects of having boosters to being fully vaccinated without them, experts have suggested that having a full round of recommended shots may offer the most protection. “My thoughts are that more shots are better, and other work has shown compelling evidence that the protective effect of vaccination on COVID-19 wanes over time,” said study coauthor Daniel Brannock, MS, a research scientist at RTI International in Research Triangle Park, N.C. “It stands to reason that the same is true for long COVID.”
• A review published in February in BMJ Medicine concluded that 10 studies showed a significant reduction in the incidence of long COVID among vaccinated patients. Even one dose of a vaccine was protective.
• A meta-analysis of six studies published last December in Antimicrobial Stewardship and Healthcare Epidemiology found that one or more doses of a COVID-19 vaccine were 29% effective in preventing symptoms of long COVID.
• In a June meta-analysis published in JAMA Internal Medicine, researchers analyzed more than 40 studies that included 860,000 patients and found that two doses of a COVID-19 vaccine reduced the risk of long COVID by almost half.

The message? COVID vaccination is very effective in reducing the risk of long COVID.

“It’s important to emphasize that many of the risk factors [for long COVID] cannot be changed, or at least cannot be changed easily, but vaccination is a decision that can be taken by everyone,” said Vassilios Vassiliou, MBBS, PhD, clinical professor of cardiac medicine at Norwich Medical School in England, who coauthored the article in JAMA Internal Medicine.
 

Why vaccines may be protective

The COVID-19 vaccines work well to prevent serious illness from the virus, noted Aaron Friedberg, MD, clinical coleader of the Post COVID Recovery Program at the Ohio State University Wexner Medical Center. That may be a clue to why the vaccines help prevent long COVID symptoms.

“When you get COVID and you’ve been vaccinated, the virus may still attach in your nose and respiratory tract, but it’s less likely to spread throughout your body,” he explained. “It’s like a forest fire – if the ground is wet or it starts to rain, it’s less likely to create a great blaze. As a result, your body is less likely to experience inflammation and damage that makes it more likely that you’ll develop long COVID.”

Dr. Friedberg stressed that even for patients who have had COVID, it’s important to get vaccinated – a message he consistently delivers to his own patients.

“There is some protection that comes from having COVID before, but for some people, that’s not enough,” he said. “It’s true that after infection, your body creates antibodies that help protect you against the virus. But I explain to patients that these may be like old Velcro: They barely grab on enough to stay on for the moment, but they don’t last long term. You’re much more likely to get a reliable immune response from the vaccine.”

In addition, a second or third bout of COVID could be the one that gives patients long COVID, Dr. Friedberg adds.

“I have a number of patients in my clinic who were fine after their first bout of COVID but experienced debilitating long COVID symptoms after they developed COVID again,” he said. “Why leave it to chance?”
 

Vaccines and ‘long vax’

The COVID vaccines are considered very safe but have been linked to very rare side effects, such as blood clots and heart inflammation. There have also been anecdotal reports of symptoms that resemble long COVID – a syndrome that has come to be known as “long Vax” – an extremely rare condition that may or may not be tied to vaccination.

“I have seen people in my clinic who developed symptoms suggestive of long COVID that linger for months – brain fog, fatigue, heart palpitations – soon after they got the COVID-19 vaccine,” said Dr. Purpura. But no published studies have suggested a link, he cautions.

A study called LISTEN is being organized at Yale in an effort to better understand postvaccine adverse events and a potential link to long COVID.
 

Talking to patients

Discussions of vaccination with patients, including those with COVID or long COVID, are often fraught and challenging, said Dr. Purpura.

“There’s a lot of fear that they will have a worsening of their symptoms,” he explained. The conversation he has with his patients mirrors the conversation all physicians should have with their patients about COVID-19 vaccination, even if they don’t have long COVID. He stresses the importance of highlighting the following components:

• Show compassion and empathy. “A lot of people have strongly held opinions – it’s worth it to try to find out why they feel the way that they do,” said Dr. Friedberg.
• Walk them through side effects. “Many people are afraid of the side effects of the vaccine, especially if they already have long COVID,” explained Dr. Purpura. Such patients can be asked how they felt after their last vaccination, such a shingles or flu shot. Then explain that the COVID-19 vaccine is not much different and that they may experience temporary side effects such as fatigue, headache, or a mild fever for 24-48 hours.
• Explain the benefits. Eighty-five percent of people say their health care provider is a trusted source of information on COVID-19 vaccines, according to the Kaiser Family Foundation. That trust is conducive to talks about the vaccine’s benefits, including its ability to protect against long COVID.

Other ways to reduce risk of long COVID

Vaccines can lower the chances of a patient’s developing long COVID. So can the antiviral medication nirmatrelvir (Paxlovid). A March 2023 study published in JAMA Internal Medicine included more than 280,000 people with COVID. The researchers found that vaccination reduced the risk for developing the condition by about 25%.

“I mention that study to all of my long COVID patients who become reinfected with the virus,” said Dr. Purpura. “It not only appears protective against long COVID, but since it lowers levels of virus circulating in their body, it seems to help prevent a flare-up of symptoms.”

Another treatment that may help is the diabetes drug metformin, he added.

A June 2023 study published in The Lancet Infectious Diseases found that when metformin was given within 3 days of symptom onset, the incidence of long COVID was reduced by about 41%.

“We’re still trying to wrap our brains around this one, but the thought is it may help to lower inflammation, which plays a role in long COVID,” Dr. Purpura explained. More studies need to be conducted, though, before recommending its use.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

TOPLINE:

Adults who take part in group-based, teacher-led mindfulness-based programs (MBPs) have reduced psychological distress.

METHODOLOGY:

Evidence suggests the effect of MBPs, which combine elements of meditation, body awareness, and modern psychology, vary as a function of individual, participant-level differences.

After a literature search, researchers selected 13 trials of in-person, teacher-led group-based MBPs that had a passive control group such as no intervention, a waitlist, or treatment-as-usual, in a total of 2,371 community adults (median age, 34 years; 71% female) who reported psychological distress levels.

Researchers conducted a systematic review and individual-participant data (IPD) meta-analysis, which allowed them to explore how intervention effects vary as a function of individual differences.

The primary outcome was self-reported psychological distress, which includes anxiety and depression, measured between 1 and 6 months after program completion using psychometrically valid questionnaires.
 

TAKEAWAY:

The trials were conducted across eight countries, had a cohort size ranging from 44 to 670 participants, and represented diverse populations including university students, law enforcement officers, and health care professionals.

Compared with passive control groups, MBPs reduced distress (standardized mean difference, –0.32; 95% CI, –0.41 to –0.24; P < .001; 95% prediction interval, –0.41 to –0.24), with no evidence of statistical heterogeneity.

Results were similar for psychological distress measured less than a month after completing the program and beyond 6 months.

There was no clear indication that baseline distress, gender, age, education level, or dispositional mindfulness (a construct reflecting an individual’s focus and quality of attention) modified the effect of MBPs on the primary outcome.
 

IN PRACTICE:

The results “encourage implementation of teacher-led MBPs for adults in nonclinical settings,” said the authors, noting that while it was difficult to ascertain clinical significance of the results because different instruments were combined, the effect size was within the range of being minimally important.

SOURCE:

The study was conducted by Julieta Galante, PhD, department of psychiatry, University of Cambridge (England), and colleagues. It was published online July 10 in Nature Mental Health.

LIMITATIONS:

The findings are limited to voluntary MBPs and don’t extend to self-guided MBPs such as those delivered through smartphone applications. Individuals with less than 12 years of education, men, and those over age 70 years were underrepresented in the dataset. The analysis was unable to consider certain effect modifiers such as participant expectations and beliefs, and personality and cognitive factors. There is risk of bias regarding the lack of blinding and self-reported outcomes, and psychological distress is an inherently subjective outcome.

DISCLOSURES:

The study received funding from the National Institute for Health Research. Dr. Galante has no relevant conflicts of interest.

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

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

We are all searching for happiness. But how do we achieve it? What are its greatest determinants?

The Harvard Study of Adult Development may be the most comprehensive study ever conducted, as it followed its participants for their entire adult lives. The study was started in Boston in 1938 and has already covered three generations: grandparents, parents, and children, who are now considered “baby boomers.” It analyzed more than 2,000 people throughout 85 years of longitudinal study.

In January, Robert J. Waldinger, MD, the current director of this incredible study, published the book The Good Life: Lessons From the World’s Longest Scientific Study of Happiness, coauthored with the study’s associate director, Marc Schulz, PhD.

By following this large population for more than 8 decades, the study uncovered the factors most correlated with well-being and happiness. Here, I have summarized some of the authors’ main concepts.
 

Most important factors

The study’s happiest participants had two major factors in common throughout its 85 years: Taking care of their health and building loving relationships with others.

It seems obvious that being in good health is essential to live well. However, to some surprise, researchers determined that good relationships were the most significant predictor of health and happiness during aging. Other authors have confirmed this finding, and research has sought to analyze the physiological mechanisms associated with this benefit.
 

Professional success insufficient

Professional success on its own does not guarantee happiness, even though it may be gratifying. The study revealed that those who were happiest were not isolated. In fact, the happiest people valued and fostered relationships. Levels of education and cultural awareness, which tend to be higher among those with higher salaries, were also important factors for adopting healthy habits (promoted more often as of the 1960s) and for better access to health care.

Social skills

Loneliness is increasingly common and creates challenges when dealing with stressful situations. It is essential to have someone with whom we can vent. Therefore, Dr. Waldinger recommends assessing how to foster, strengthen, and broaden relationships. He calls this maintaining social connections and, just as with physical fitness, it also requires constant practice. Friendships and relationships need regular commitment to keep them from fizzling out. A simple telephone call can help. Participating in activities that bring joy and encourage camaraderie, such as sports, hobbies, and volunteer work, may broaden the relationship network.

Happiness not constant

Social media almost always shows the positive side of people’s lives and suggests that everyone lives worry-free. However, the truth is that no one’s life is free of difficulties and challenges. Social skills contribute to resilience.

It is never too late for a turnaround and for people to change their lives through new relationships and experiences. Those who think they know everything about life are very mistaken. The study showed that good things happened to those who had given up on changing their situation, and good news appeared when they least expected it.

This study highlights the importance of having social skills and always cultivating our relationships to help us become healthier, overcome challenging moments, and achieve the happiness that we all desire.

We finally have robust evidence-based data to use when speaking on happiness.

Dr. Wajngarten is professor of cardiology, University of São Paulo, Brazil. He has disclosed no relevant financial relationships.

This article was translated from the Medscape Portuguese Edition. A version of this article appeared on Medscape.com.

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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

The antiplatelet of choice for long-term, secondary prevention for patients with established coronary artery disease (CAD) may well be a P2Y12 inhibitor such as clopidogrel or ticagrelor rather than aspirin, suggests a patient-level meta-analysis of seven randomized trials.

The more than 24,000 patients in the meta-analysis, called PANTHER, had documented stable CAD, prior myocardial infarction (MI), or recent or remote surgical or percutaneous coronary revascularization.

About half of patients in each antiplatelet monotherapy trial received clopidogrel or ticagrelor, and the other half received aspirin. Follow-ups ranged from 6 months to 3 years.

Those taking a P2Y12 inhibitor showed a 12% reduction in risk (P = .012) for the primary efficacy outcome, a composite of cardiovascular (CV) death, MI, and stroke, over a median of about 1.35 years. The difference was driven primarily by a 23% reduction in risk for MI (P < .001); mortality seemed unaffected by antiplatelet treatment assignment.

Although the P2Y12 inhibitor and aspirin groups were similar with respect to risk of major bleeding, the P2Y12 inhibitor group showed significant reductions in risk for gastrointestinal (GI) bleeding, definite stent thrombosis, and hemorrhagic stroke; rates of hemorrhagic stroke were well under 1% in both groups.

The treatment effects were consistent across patient subgroups, including whether the aspirin comparison was with clopidogrel or ticagrelor.

“Taken together, our data challenge the central role of aspirin in secondary prevention and support a paradigm shift toward P2Y12 inhibitor monotherapy as long-term antiplatelet strategy in the sizable population of patients with coronary atherosclerosis,” Felice Gragnano, MD, PhD, said in an interview. “Given [their] superior efficacy and similar overall safety, P2Y12 inhibitors may be preferred [over] aspirin for the prevention of cardiovascular events in patients with CAD.”

Dr. Gragnano, of the University of Campania Luigi Vanvitelli, Caserta, Italy, who called PANTHER “the largest and most comprehensive synthesis of individual patient data from randomized trials comparing P2Y12 inhibitor monotherapy with aspirin monotherapy,” is lead author of the study, which was published online in the Journal of the American College of Cardiology.

Current guidelines recommend aspirin for antiplatelet monotherapy for patients with established CAD, Dr. Gragnano said, but “the primacy of aspirin in secondary prevention is based on historical trials conducted in the 1970s and 1980s and may not apply to contemporary practice.”

Moreover, later trials that compared P2Y12 inhibitors with aspirin for secondary prevention produced “inconsistent results,” possibly owing to their heterogeneous populations of patients with coronary, cerebrovascular, or peripheral vascular disease, he said. Study-level meta-analyses in this area “provide inconclusive evidence” because they haven’t evaluated treatment effects exclusively in patients with established CAD.

Most of the seven trials’ 24,325 participants had a history of MI, and some had peripheral artery disease (PAD); the rates were 56.2% and 9.1%, respectively. Coronary revascularization, either percutaneous or surgical, had been performed for about 70%. Most (61%) had presented with acute coronary syndromes, and the remainder had presented with chronic CAD.

About 76% of the combined cohorts were from Europe or North America; the rest were from Asia. The mean age of the patients was 64 years, and about 22% were women.

In all, 12,175 had been assigned to P2Y12 inhibitor monotherapy (62% received clopidogrel and 38% received ticagrelor); 12,147 received aspirin at dosages ranging from 75 mg to 325 mg daily.

The hazard ratio (HR) for the primary efficacy outcome, P2Y12 inhibitors vs. aspirin, was significantly reduced, at 0.88 (95% confidence interval [CI], 0.79-0.97; P = .012); the number needed to treat (NNT) to prevent one primary event over 2 years was 121, the report states.

The corresponding HR for MI was 0.77 (95% CI, 0.66-0.90; P < .001), for an NNT benefit of 136. For net adverse clinical events, the HR was 0.89 (95% CI, 0.81-0.98; P = .020), for an NNT benefit of 121.

Risk for major bleeding was not significantly different (HR, 0.87; 95% CI, 0.70-1.09; P = .23), nor were risks for stroke (HR, 0.84; 95% CI, 0.70-1.02; P = .076) or cardiovascular death (HR, 1.02; 95% CI, 0.86-1.20; P = .82).

Still, the P2Y12 inhibitor group showed significant risk reductions for the following:

• GI bleeding: HR, 0.75 (95% CI, 0.57-0.97; P = .027)
• Definite stent thrombosis: HR, 0.42 (95% CI, 0.19-0.97; P = .028)
• Hemorrhagic stroke: HR, 0.43 (95% CI, 0.23-0.83; P = .012)

The current findings are “hypothesis-generating but not definitive,” Dharam Kumbhani, MD, University of Texas Southwestern, Dallas, said in an interview.

It remains unclear “whether aspirin or P2Y12 inhibitor monotherapy is better for long-term maintenance use among patients with established CAD. Aspirin has historically been the agent of choice for this indication,” said Dr. Kumbhani, who with James A. de Lemos, MD, of the same institution, wrote an editorial accompanying the PANTHER report.

“It certainly would be appropriate to consider P2Y12 monotherapy preferentially for patients with prior or currently at high risk for GI or intracranial bleeding, for instance,” Dr. Kumbhani said. For the remainder, aspirin and P2Y12 inhibitors are both “reasonable alternatives.”

In their editorial, Dr. Kumbhani and Dr. de Lemos call the PANTHER meta-analysis “a well-done study with potentially important clinical implications.” The findings “make biological sense: P2Y12 inhibitors are more potent antiplatelet agents than aspirin and have less effect on gastrointestinal mucosal integrity.”

But for now, they wrote, “both aspirin and P2Y12 inhibitors remain viable alternatives for prevention of atherothrombotic events among patients with established CAD.”

Dr. Gragnano had no disclosures; potential conflicts for the other authors are in the report. Dr. Kumbhani reports no relevant relationships; Dr. de Lemos has received honoraria for participation in data safety monitoring boards from Eli Lilly, Novo Nordisk, AstraZeneca, and Janssen.

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