This article was originally published in Italian on Univadis .

The arrival of Ukrainian refugees in Western Europe, and especially the arrival of women and children coming from the cities most affected by the attacks, has made local medical services the first point of contact for the diagnosis and care of the psychological effects of war.

Many studies demonstrate the high prevalence of posttraumatic stress disorder (PTSD), depression, and anxiety among refugees. For example, a study from 2019 on refugee mental health offers a disturbing epidemiologic insight: Ten percent of refugees escaping conflict in Nepal showed signs of PTSD, 27.5% suffered from depression, and 22.9% suffered from anxiety. The rate of depression surpasses 90% in all studies carried out on survivors of torture.
 

Official guidelines

Posttraumatic stress is a form of mental disorder that manifests after experiencing highly traumatic events. Defined and studied in the United States, especially in veterans of the Vietnam War, and subsequently reviewed in relation to more recent conflicts, PTSD may appear in people of all ages. It also can occur in family members, witnesses, and aid workers involved in traumatic events. PTSD may come from repeated exposure to episodes of violence and degradation.

Because PTSD is a complex mental disorder derived from multiple factors, both personal and environmental, a diagnosis is never straightforward. It is generally indicated as “a condition of acute stress which manifests after exposure to a traumatic event.”

Among the most common symptoms of war-related trauma, according to experts, are the onset of flashbacks of troublesome memories, intrusive trauma-related thoughts, panic attacks, insomnia and night terrors, and social avoidance. In children, elements of regression can be observed, such as a need to sleep next to their parents.

Research performed directly on different areas of the brain has demonstrated that people affected by PTSD produce abnormal levels of hormones that are involved in responding to stress and fear. The area of the brain responsible for this response is the amygdala, which activates during moments of fear and produces natural pain-relieving molecules. In people with PTSD, the production of these molecules can carry on long after the event is over, causing a change in emotional state. Furthermore, levels of neurotransmitters that reach the hippocampus are also altered, which influences memory and learning capability. These same alterations concerning neurotransmitter levels are the basis for sudden flashbacks.

People with PTSD are subject to a change in blood flow to the brain and structural changes to brain tissue.
 

Social factors

“A factor that worsens the mental condition of Ukrainian refugees is the speed in which they have passed from a normal life, similar to that of many other Western countries, to a state of war, death, and injury,” writes Arash Javanbakht, MD, associate professor of psychiatry at Wayne State University in Detroit, and an expert in PTSD in war refugees.

Courtesy Shantanu Madaboosi

“Furthermore, they are experiencing an awful feeling of injustice, as the democracy and freedom that they have fought so hard to have has been put at risk, and they don’t feel sufficiently supported by their allies.”

As of this writing, the World Health Organization has estimated that there are 3.6 million Ukrainian refugees. This population already has experienced war and its psychological consequences. A study from 2019 assessed the prevalence of PTSD (27%) and depression (21%) among the 1.5 million Ukrainians who had to leave their homes after the first Russian invasion in 2014 and the rebellion of predominantly Russian regions.

Children are particularly at risk of developing PTSD, as seen from studies conducted on Syrian refugees. They have a roughly 70% chance of developing separation anxiety, a condition that many workers and volunteers have experienced firsthand recently. Some children do not accept being separated from their parents even to allow them to go to the bathroom or wash themselves, which also aggravates stress levels among adults. Infant trauma increases the risk of developing physical or mental disorders during adulthood, including depression, chronic pain, heart disorders, and diabetes.

War-related trauma entails transmissible epigenetic alterations, as shown by studies on the transmissibility of trauma on a biological level.
 

Diagnosis and treatment

People with PTSD have difficulty controlling their emotions, resulting in irritability, sudden rage or emotional confusion, depression and anxiety, and insomnia. They also are determined to avoid any actions that remind them of the traumatic event. Another common symptom is a sense of shame, as a result of having survived or not having been able to save others.

Physical symptoms include chest pain, dizziness, gastrointestinal problems, migraine, and a weakened immune system. A diagnosis of PTSD can be made when, in accordance with the National Institute of Mental Health (NIMH), the patient presents with the characteristic symptoms for more than a month after the event that caused the symptoms occurred.

The NIMH highlights that a diagnosis cannot always be made in a systematic way. In many cases, patients with PTSD are treated for the physical symptoms only, without any consideration for the overall picture.

The American Psychiatric Association (APA) has created a detailed list of PTSD symptoms. According to the APA, these symptoms usually appear within 3 months of the trauma, even if stress may appear later. Symptoms are arranged into the following three well-defined categories:

• Intrusive memories. People with PTSD suffer from sudden, vivid memories that are accompanied by painful emotions and a feeling of reliving the trauma. At times, this experience is so strong that the person involved feels as though the traumatic event is repeating itself.
• Avoidance and numbing. The individual seeks to avoid contact with anyone or anything that brings back memories of the trauma. Initially, the person experiences an emotional state of disinterest and detachment, reducing the capacity for emotional interaction and resulting in participation only in simple, routine activities. A lack of emotional processing causes an accumulation of anxiety and tension, which can become a chronic condition, leading to depression. At the same time, people frequently experience a sense of shame.
• Hyperarousal and hypervigilance. People behave as if they are constantly threatened. They react in a sudden, violent way, are unable to concentrate, and have problems with their memory. At times, they use alcohol or other drugs to alleviate pain. People with PTSD may lose control of their lives and therefore be at risk for suicidal behavior.

Why do some people pass unscathed through traumatic situations, whereas others carry the scars forever? There is a correlation with the severity of the trauma, but also with biological and genetic factors, as well as with previous experiences that contribute to increasing an individual’s resilience. Another key element is the rapid and effective treatment of symptoms, which also relates to personal and financial security.

It is not a coincidence that the first guidelines that clinicians follow when treating a traumatized patient aren’t strictly medical. It is necessary to guarantee the financial security of a refugee, but also the security of the few valuable items they have with them (such as keepsakes and pets). Clinicians are advised to facilitate contact with any of the patient’s family members located elsewhere whenever possible. It is appropriate to use relaxation techniques that are compatible with the patient’s cultural approach. Clinicians also check for the most common conditions in the refugee’s population of origin. It is advisable constantly to check for trauma-related symptoms and to listen to the patient’s story. Caregivers should be allowed to stay close to their children and should be provided sufficient information, but not an overwhelming amount.

There isn’t a consensus on how to treat people with PTSD. The possibility that PTSD can be resolved even without specific treatments has not been excluded, if the affected person is cared for and helped within a family and community setting, and if the person’s personal condition allows for this. However, in general, some form of treatment is beneficial before symptoms become chronic.

Pharmacologic and psychological treatment may be implemented. For the latter, the NIMH and the APA suggest that good results can be obtained from cognitive behavioral therapy, where the patient learns to manage his or her anxiety and depression and amend dangerous behaviors, such as the dismissal of his or her own emotions. According to these organizations, group therapy and other forms of psychotherapy have provided good results. The indicated duration of treatment is generally 6-12 weeks, even if this duration strongly depends on the individual’s condition, with subsequent periodic follow-ups. The involvement of the patient’s family and community is important.

The National Center for PTSD in Washington (run by the U.S. Department of Veterans Affairs) has highlighted the importance of a detailed case-by-case assessment to put in place a precise therapy plan. If patients should continue to find themselves in a state of crisis, for example during a war or in cases of domestic violence, working toward removing the cause of stress is first necessary before beginning treatment.

An important aspect is making the victim aware of the disorder. Treatment should therefore begin after the patient and family have been informed about the possibility of PTSD and the way in which it develops. Recognizing the symptoms over the following weeks and working quickly to manage and treat them significantly affects treatment success.

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

This article was originally published in Italian on Univadis .

The arrival of Ukrainian refugees in Western Europe, and especially the arrival of women and children coming from the cities most affected by the attacks, has made local medical services the first point of contact for the diagnosis and care of the psychological effects of war.

Many studies demonstrate the high prevalence of posttraumatic stress disorder (PTSD), depression, and anxiety among refugees. For example, a study from 2019 on refugee mental health offers a disturbing epidemiologic insight: Ten percent of refugees escaping conflict in Nepal showed signs of PTSD, 27.5% suffered from depression, and 22.9% suffered from anxiety. The rate of depression surpasses 90% in all studies carried out on survivors of torture.
 

Official guidelines

Posttraumatic stress is a form of mental disorder that manifests after experiencing highly traumatic events. Defined and studied in the United States, especially in veterans of the Vietnam War, and subsequently reviewed in relation to more recent conflicts, PTSD may appear in people of all ages. It also can occur in family members, witnesses, and aid workers involved in traumatic events. PTSD may come from repeated exposure to episodes of violence and degradation.

Because PTSD is a complex mental disorder derived from multiple factors, both personal and environmental, a diagnosis is never straightforward. It is generally indicated as “a condition of acute stress which manifests after exposure to a traumatic event.”

Among the most common symptoms of war-related trauma, according to experts, are the onset of flashbacks of troublesome memories, intrusive trauma-related thoughts, panic attacks, insomnia and night terrors, and social avoidance. In children, elements of regression can be observed, such as a need to sleep next to their parents.

Research performed directly on different areas of the brain has demonstrated that people affected by PTSD produce abnormal levels of hormones that are involved in responding to stress and fear. The area of the brain responsible for this response is the amygdala, which activates during moments of fear and produces natural pain-relieving molecules. In people with PTSD, the production of these molecules can carry on long after the event is over, causing a change in emotional state. Furthermore, levels of neurotransmitters that reach the hippocampus are also altered, which influences memory and learning capability. These same alterations concerning neurotransmitter levels are the basis for sudden flashbacks.

People with PTSD are subject to a change in blood flow to the brain and structural changes to brain tissue.
 

Social factors

“A factor that worsens the mental condition of Ukrainian refugees is the speed in which they have passed from a normal life, similar to that of many other Western countries, to a state of war, death, and injury,” writes Arash Javanbakht, MD, associate professor of psychiatry at Wayne State University in Detroit, and an expert in PTSD in war refugees.

Courtesy Shantanu Madaboosi

“Furthermore, they are experiencing an awful feeling of injustice, as the democracy and freedom that they have fought so hard to have has been put at risk, and they don’t feel sufficiently supported by their allies.”

As of this writing, the World Health Organization has estimated that there are 3.6 million Ukrainian refugees. This population already has experienced war and its psychological consequences. A study from 2019 assessed the prevalence of PTSD (27%) and depression (21%) among the 1.5 million Ukrainians who had to leave their homes after the first Russian invasion in 2014 and the rebellion of predominantly Russian regions.

Children are particularly at risk of developing PTSD, as seen from studies conducted on Syrian refugees. They have a roughly 70% chance of developing separation anxiety, a condition that many workers and volunteers have experienced firsthand recently. Some children do not accept being separated from their parents even to allow them to go to the bathroom or wash themselves, which also aggravates stress levels among adults. Infant trauma increases the risk of developing physical or mental disorders during adulthood, including depression, chronic pain, heart disorders, and diabetes.

War-related trauma entails transmissible epigenetic alterations, as shown by studies on the transmissibility of trauma on a biological level.
 

Diagnosis and treatment

People with PTSD have difficulty controlling their emotions, resulting in irritability, sudden rage or emotional confusion, depression and anxiety, and insomnia. They also are determined to avoid any actions that remind them of the traumatic event. Another common symptom is a sense of shame, as a result of having survived or not having been able to save others.

Physical symptoms include chest pain, dizziness, gastrointestinal problems, migraine, and a weakened immune system. A diagnosis of PTSD can be made when, in accordance with the National Institute of Mental Health (NIMH), the patient presents with the characteristic symptoms for more than a month after the event that caused the symptoms occurred.

The NIMH highlights that a diagnosis cannot always be made in a systematic way. In many cases, patients with PTSD are treated for the physical symptoms only, without any consideration for the overall picture.

The American Psychiatric Association (APA) has created a detailed list of PTSD symptoms. According to the APA, these symptoms usually appear within 3 months of the trauma, even if stress may appear later. Symptoms are arranged into the following three well-defined categories:

• Intrusive memories. People with PTSD suffer from sudden, vivid memories that are accompanied by painful emotions and a feeling of reliving the trauma. At times, this experience is so strong that the person involved feels as though the traumatic event is repeating itself.
• Avoidance and numbing. The individual seeks to avoid contact with anyone or anything that brings back memories of the trauma. Initially, the person experiences an emotional state of disinterest and detachment, reducing the capacity for emotional interaction and resulting in participation only in simple, routine activities. A lack of emotional processing causes an accumulation of anxiety and tension, which can become a chronic condition, leading to depression. At the same time, people frequently experience a sense of shame.
• Hyperarousal and hypervigilance. People behave as if they are constantly threatened. They react in a sudden, violent way, are unable to concentrate, and have problems with their memory. At times, they use alcohol or other drugs to alleviate pain. People with PTSD may lose control of their lives and therefore be at risk for suicidal behavior.

Why do some people pass unscathed through traumatic situations, whereas others carry the scars forever? There is a correlation with the severity of the trauma, but also with biological and genetic factors, as well as with previous experiences that contribute to increasing an individual’s resilience. Another key element is the rapid and effective treatment of symptoms, which also relates to personal and financial security.

It is not a coincidence that the first guidelines that clinicians follow when treating a traumatized patient aren’t strictly medical. It is necessary to guarantee the financial security of a refugee, but also the security of the few valuable items they have with them (such as keepsakes and pets). Clinicians are advised to facilitate contact with any of the patient’s family members located elsewhere whenever possible. It is appropriate to use relaxation techniques that are compatible with the patient’s cultural approach. Clinicians also check for the most common conditions in the refugee’s population of origin. It is advisable constantly to check for trauma-related symptoms and to listen to the patient’s story. Caregivers should be allowed to stay close to their children and should be provided sufficient information, but not an overwhelming amount.

There isn’t a consensus on how to treat people with PTSD. The possibility that PTSD can be resolved even without specific treatments has not been excluded, if the affected person is cared for and helped within a family and community setting, and if the person’s personal condition allows for this. However, in general, some form of treatment is beneficial before symptoms become chronic.

Pharmacologic and psychological treatment may be implemented. For the latter, the NIMH and the APA suggest that good results can be obtained from cognitive behavioral therapy, where the patient learns to manage his or her anxiety and depression and amend dangerous behaviors, such as the dismissal of his or her own emotions. According to these organizations, group therapy and other forms of psychotherapy have provided good results. The indicated duration of treatment is generally 6-12 weeks, even if this duration strongly depends on the individual’s condition, with subsequent periodic follow-ups. The involvement of the patient’s family and community is important.

The National Center for PTSD in Washington (run by the U.S. Department of Veterans Affairs) has highlighted the importance of a detailed case-by-case assessment to put in place a precise therapy plan. If patients should continue to find themselves in a state of crisis, for example during a war or in cases of domestic violence, working toward removing the cause of stress is first necessary before beginning treatment.

An important aspect is making the victim aware of the disorder. Treatment should therefore begin after the patient and family have been informed about the possibility of PTSD and the way in which it develops. Recognizing the symptoms over the following weeks and working quickly to manage and treat them significantly affects treatment success.

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

This article was originally published in Italian on Univadis .

The arrival of Ukrainian refugees in Western Europe, and especially the arrival of women and children coming from the cities most affected by the attacks, has made local medical services the first point of contact for the diagnosis and care of the psychological effects of war.

Many studies demonstrate the high prevalence of posttraumatic stress disorder (PTSD), depression, and anxiety among refugees. For example, a study from 2019 on refugee mental health offers a disturbing epidemiologic insight: Ten percent of refugees escaping conflict in Nepal showed signs of PTSD, 27.5% suffered from depression, and 22.9% suffered from anxiety. The rate of depression surpasses 90% in all studies carried out on survivors of torture.
 

Official guidelines

Posttraumatic stress is a form of mental disorder that manifests after experiencing highly traumatic events. Defined and studied in the United States, especially in veterans of the Vietnam War, and subsequently reviewed in relation to more recent conflicts, PTSD may appear in people of all ages. It also can occur in family members, witnesses, and aid workers involved in traumatic events. PTSD may come from repeated exposure to episodes of violence and degradation.

Because PTSD is a complex mental disorder derived from multiple factors, both personal and environmental, a diagnosis is never straightforward. It is generally indicated as “a condition of acute stress which manifests after exposure to a traumatic event.”

Among the most common symptoms of war-related trauma, according to experts, are the onset of flashbacks of troublesome memories, intrusive trauma-related thoughts, panic attacks, insomnia and night terrors, and social avoidance. In children, elements of regression can be observed, such as a need to sleep next to their parents.

Research performed directly on different areas of the brain has demonstrated that people affected by PTSD produce abnormal levels of hormones that are involved in responding to stress and fear. The area of the brain responsible for this response is the amygdala, which activates during moments of fear and produces natural pain-relieving molecules. In people with PTSD, the production of these molecules can carry on long after the event is over, causing a change in emotional state. Furthermore, levels of neurotransmitters that reach the hippocampus are also altered, which influences memory and learning capability. These same alterations concerning neurotransmitter levels are the basis for sudden flashbacks.

People with PTSD are subject to a change in blood flow to the brain and structural changes to brain tissue.
 

Social factors

“A factor that worsens the mental condition of Ukrainian refugees is the speed in which they have passed from a normal life, similar to that of many other Western countries, to a state of war, death, and injury,” writes Arash Javanbakht, MD, associate professor of psychiatry at Wayne State University in Detroit, and an expert in PTSD in war refugees.

Courtesy Shantanu Madaboosi

“Furthermore, they are experiencing an awful feeling of injustice, as the democracy and freedom that they have fought so hard to have has been put at risk, and they don’t feel sufficiently supported by their allies.”

As of this writing, the World Health Organization has estimated that there are 3.6 million Ukrainian refugees. This population already has experienced war and its psychological consequences. A study from 2019 assessed the prevalence of PTSD (27%) and depression (21%) among the 1.5 million Ukrainians who had to leave their homes after the first Russian invasion in 2014 and the rebellion of predominantly Russian regions.

Children are particularly at risk of developing PTSD, as seen from studies conducted on Syrian refugees. They have a roughly 70% chance of developing separation anxiety, a condition that many workers and volunteers have experienced firsthand recently. Some children do not accept being separated from their parents even to allow them to go to the bathroom or wash themselves, which also aggravates stress levels among adults. Infant trauma increases the risk of developing physical or mental disorders during adulthood, including depression, chronic pain, heart disorders, and diabetes.

War-related trauma entails transmissible epigenetic alterations, as shown by studies on the transmissibility of trauma on a biological level.
 

Diagnosis and treatment

People with PTSD have difficulty controlling their emotions, resulting in irritability, sudden rage or emotional confusion, depression and anxiety, and insomnia. They also are determined to avoid any actions that remind them of the traumatic event. Another common symptom is a sense of shame, as a result of having survived or not having been able to save others.

Physical symptoms include chest pain, dizziness, gastrointestinal problems, migraine, and a weakened immune system. A diagnosis of PTSD can be made when, in accordance with the National Institute of Mental Health (NIMH), the patient presents with the characteristic symptoms for more than a month after the event that caused the symptoms occurred.

The NIMH highlights that a diagnosis cannot always be made in a systematic way. In many cases, patients with PTSD are treated for the physical symptoms only, without any consideration for the overall picture.

The American Psychiatric Association (APA) has created a detailed list of PTSD symptoms. According to the APA, these symptoms usually appear within 3 months of the trauma, even if stress may appear later. Symptoms are arranged into the following three well-defined categories:

• Intrusive memories. People with PTSD suffer from sudden, vivid memories that are accompanied by painful emotions and a feeling of reliving the trauma. At times, this experience is so strong that the person involved feels as though the traumatic event is repeating itself.
• Avoidance and numbing. The individual seeks to avoid contact with anyone or anything that brings back memories of the trauma. Initially, the person experiences an emotional state of disinterest and detachment, reducing the capacity for emotional interaction and resulting in participation only in simple, routine activities. A lack of emotional processing causes an accumulation of anxiety and tension, which can become a chronic condition, leading to depression. At the same time, people frequently experience a sense of shame.
• Hyperarousal and hypervigilance. People behave as if they are constantly threatened. They react in a sudden, violent way, are unable to concentrate, and have problems with their memory. At times, they use alcohol or other drugs to alleviate pain. People with PTSD may lose control of their lives and therefore be at risk for suicidal behavior.

Why do some people pass unscathed through traumatic situations, whereas others carry the scars forever? There is a correlation with the severity of the trauma, but also with biological and genetic factors, as well as with previous experiences that contribute to increasing an individual’s resilience. Another key element is the rapid and effective treatment of symptoms, which also relates to personal and financial security.

It is not a coincidence that the first guidelines that clinicians follow when treating a traumatized patient aren’t strictly medical. It is necessary to guarantee the financial security of a refugee, but also the security of the few valuable items they have with them (such as keepsakes and pets). Clinicians are advised to facilitate contact with any of the patient’s family members located elsewhere whenever possible. It is appropriate to use relaxation techniques that are compatible with the patient’s cultural approach. Clinicians also check for the most common conditions in the refugee’s population of origin. It is advisable constantly to check for trauma-related symptoms and to listen to the patient’s story. Caregivers should be allowed to stay close to their children and should be provided sufficient information, but not an overwhelming amount.

There isn’t a consensus on how to treat people with PTSD. The possibility that PTSD can be resolved even without specific treatments has not been excluded, if the affected person is cared for and helped within a family and community setting, and if the person’s personal condition allows for this. However, in general, some form of treatment is beneficial before symptoms become chronic.

Pharmacologic and psychological treatment may be implemented. For the latter, the NIMH and the APA suggest that good results can be obtained from cognitive behavioral therapy, where the patient learns to manage his or her anxiety and depression and amend dangerous behaviors, such as the dismissal of his or her own emotions. According to these organizations, group therapy and other forms of psychotherapy have provided good results. The indicated duration of treatment is generally 6-12 weeks, even if this duration strongly depends on the individual’s condition, with subsequent periodic follow-ups. The involvement of the patient’s family and community is important.

The National Center for PTSD in Washington (run by the U.S. Department of Veterans Affairs) has highlighted the importance of a detailed case-by-case assessment to put in place a precise therapy plan. If patients should continue to find themselves in a state of crisis, for example during a war or in cases of domestic violence, working toward removing the cause of stress is first necessary before beginning treatment.

An important aspect is making the victim aware of the disorder. Treatment should therefore begin after the patient and family have been informed about the possibility of PTSD and the way in which it develops. Recognizing the symptoms over the following weeks and working quickly to manage and treat them significantly affects treatment success.

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

New cases of COVID-19 in U.S. children went up for a second consecutive week, but the pace of increase slowed considerably, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New pediatric cases were up by 11.8% for the week of April 15-21, with a total of just over 37,000 reported. The previous week’s count – about 33,000 new COVID cases for April 8-14 – was almost 30% higher than the week before and marked the first rise in incidence after 11 straight weeks of declines, the AAP and CHA said in their weekly COVID-19 report, which is based on data from state and territorial health departments.

The cumulative number of child COVID-19 cases since the start of the pandemic is now over 12.9 million, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention, which uses a different age range for children (0-17 years) than many states, reports corresponding figures of 12.4 million and 17.6%, along with 1,501 deaths.

ED visits show a similar rising trend over recent weeks, as the 7-day average of ED visits with confirmed COVID has crept up from 0.5% in late March/early April to 0.8% on April 22 for children aged 0-11 years, from 0.3% for 0.5% for those aged 12-15, and from 0.3% to 0.6% for 16- and 17-year-olds, based on CDC data.

The daily rate for new admissions for children with confirmed COVID has also moved up slightly, rising from 0.13 per 100,000 population as late as April 13 to 0.15 per 100,000 on April 23. For the number of actual admissions, the latest 7-day (April 17-23) average was 107 in children aged 0-17, compared with 102 for the week of April 10-16, the CDC reported.

Uptake of the COVID vaccine, however, continued to slide since spiking in January. Initial vaccinations for the latest available week (April 14-20) were down to 48,000 from 59,000 the week before in children aged 5-11 years and 35,000 (vs. 47,000) for those aged 12-17. The weekly highs hit 500,000 and 331,000, respectively, during the Omicron surge, the AAP reported based on CDC data.

Among children aged 5-11, the CDC said that 35.0% had received at least one dose of COVID vaccine as of April 25 and that 28.3% are fully vaccinated, with corresponding figures of 68.8% and 58.8% for 12- to 17-year-olds on April 25.

Among the states, the highest vaccination rates generally are found in New England and the lowest in the Southeast. In Alabama, just 15% of children aged 5-11 have received an initial dose of the vaccine, compared with 66% in Vermont, while Wyoming is the lowest (41%) for children aged 12-17 and Massachusetts is the highest (96%), the AAP said in a separate report.

rfranki@mdedge.com

New cases of COVID-19 in U.S. children went up for a second consecutive week, but the pace of increase slowed considerably, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New pediatric cases were up by 11.8% for the week of April 15-21, with a total of just over 37,000 reported. The previous week’s count – about 33,000 new COVID cases for April 8-14 – was almost 30% higher than the week before and marked the first rise in incidence after 11 straight weeks of declines, the AAP and CHA said in their weekly COVID-19 report, which is based on data from state and territorial health departments.

The cumulative number of child COVID-19 cases since the start of the pandemic is now over 12.9 million, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention, which uses a different age range for children (0-17 years) than many states, reports corresponding figures of 12.4 million and 17.6%, along with 1,501 deaths.

ED visits show a similar rising trend over recent weeks, as the 7-day average of ED visits with confirmed COVID has crept up from 0.5% in late March/early April to 0.8% on April 22 for children aged 0-11 years, from 0.3% for 0.5% for those aged 12-15, and from 0.3% to 0.6% for 16- and 17-year-olds, based on CDC data.

The daily rate for new admissions for children with confirmed COVID has also moved up slightly, rising from 0.13 per 100,000 population as late as April 13 to 0.15 per 100,000 on April 23. For the number of actual admissions, the latest 7-day (April 17-23) average was 107 in children aged 0-17, compared with 102 for the week of April 10-16, the CDC reported.

Uptake of the COVID vaccine, however, continued to slide since spiking in January. Initial vaccinations for the latest available week (April 14-20) were down to 48,000 from 59,000 the week before in children aged 5-11 years and 35,000 (vs. 47,000) for those aged 12-17. The weekly highs hit 500,000 and 331,000, respectively, during the Omicron surge, the AAP reported based on CDC data.

Among children aged 5-11, the CDC said that 35.0% had received at least one dose of COVID vaccine as of April 25 and that 28.3% are fully vaccinated, with corresponding figures of 68.8% and 58.8% for 12- to 17-year-olds on April 25.

Among the states, the highest vaccination rates generally are found in New England and the lowest in the Southeast. In Alabama, just 15% of children aged 5-11 have received an initial dose of the vaccine, compared with 66% in Vermont, while Wyoming is the lowest (41%) for children aged 12-17 and Massachusetts is the highest (96%), the AAP said in a separate report.

rfranki@mdedge.com

New cases of COVID-19 in U.S. children went up for a second consecutive week, but the pace of increase slowed considerably, based on a report from the American Academy of Pediatrics and the Children’s Hospital Association.

New pediatric cases were up by 11.8% for the week of April 15-21, with a total of just over 37,000 reported. The previous week’s count – about 33,000 new COVID cases for April 8-14 – was almost 30% higher than the week before and marked the first rise in incidence after 11 straight weeks of declines, the AAP and CHA said in their weekly COVID-19 report, which is based on data from state and territorial health departments.

The cumulative number of child COVID-19 cases since the start of the pandemic is now over 12.9 million, with children representing 19.0% of cases among all ages. The Centers for Disease Control and Prevention, which uses a different age range for children (0-17 years) than many states, reports corresponding figures of 12.4 million and 17.6%, along with 1,501 deaths.

ED visits show a similar rising trend over recent weeks, as the 7-day average of ED visits with confirmed COVID has crept up from 0.5% in late March/early April to 0.8% on April 22 for children aged 0-11 years, from 0.3% for 0.5% for those aged 12-15, and from 0.3% to 0.6% for 16- and 17-year-olds, based on CDC data.

The daily rate for new admissions for children with confirmed COVID has also moved up slightly, rising from 0.13 per 100,000 population as late as April 13 to 0.15 per 100,000 on April 23. For the number of actual admissions, the latest 7-day (April 17-23) average was 107 in children aged 0-17, compared with 102 for the week of April 10-16, the CDC reported.

Uptake of the COVID vaccine, however, continued to slide since spiking in January. Initial vaccinations for the latest available week (April 14-20) were down to 48,000 from 59,000 the week before in children aged 5-11 years and 35,000 (vs. 47,000) for those aged 12-17. The weekly highs hit 500,000 and 331,000, respectively, during the Omicron surge, the AAP reported based on CDC data.

Among children aged 5-11, the CDC said that 35.0% had received at least one dose of COVID vaccine as of April 25 and that 28.3% are fully vaccinated, with corresponding figures of 68.8% and 58.8% for 12- to 17-year-olds on April 25.

Among the states, the highest vaccination rates generally are found in New England and the lowest in the Southeast. In Alabama, just 15% of children aged 5-11 have received an initial dose of the vaccine, compared with 66% in Vermont, while Wyoming is the lowest (41%) for children aged 12-17 and Massachusetts is the highest (96%), the AAP said in a separate report.

rfranki@mdedge.com

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

People aged 65 or older with human immunodeficiency virus (HIV) receive significantly more nonantiretroviral therapy (non-ART) medications, compared with patients with HIV who are between ages 50 and 64, according to a new study.

Moreover, in a sample of more than 900 patients with HIV, about 60% were taking at least one potentially inappropriate medication (PIM).

“Clinicians looking after persons living with HIV need to provide medication reconciliation with prioritization of medications based on the patients’ wishes and patients’ goals and life expectancy,” lead author Jacqueline McMillan, MD, clinical assistant professor of geriatric medicine at the University of Calgary (Alt.) told this news organization.

The findings were published online in the Canadian Journal of General Internal Medicine.
 

Examining the pill burden

A geriatrician by training and a clinical researcher with an interest in aging in patients with HIV, Dr. McMillan said she began to observe that many older adults with HIV were on polypharmacy. “There are many other things that aging people with HIV experience, such as frailty, falls, cognitive impairment, medication nonadherence, and mortality, but in this study, we focused just on the polypharmacy,” said Dr. McMillan.

Her aim was to see if there was a way to improve the pill burden in these older adults.

“Do they need to be on all of these medications? Is there anything that we were overprescribing that they no longer needed, or possibly not prescribing and undertreating people because they were older? I wanted to have a better sense that the medications we were prescribing were appropriate and that we minimized the pill burden for older adults,” Dr. McMillan said.

Persons with HIV are at a particularly increased risk of polypharmacy and potential drug-drug interactions because they need antiretroviral therapy medications and medications to treat comorbidities.

“Certainly, when the ARTs were first discovered, sometimes that regimen required several pills a day, but as time has gone on and our retrovirals have gotten better, some of those requirements have narrowed down to one-pill-a-day regimens. We are now replacing that pill burden with non-HIV drugs,” said Dr. McMillan.

The researchers obtained medication reconciliation data for 951 persons with HIV aged 50 or older as of Feb. 1, 2020. The study population was receiving HIV care through the Southern Alberta HIV Clinic in Calgary. The researchers defined polypharmacy as taking five or more non-ART drugs. They defined PIMs according to the 2019 Beers criteria.

In their analysis, the researchers compared patients aged 65 or older with patients aged 50-64, as well as patients with shorter (< 10 years) and longer (> 10 years) duration of HIV infection.
 

PIM use common

The population’s mean age was 59 years, and 82% were men. The mean time since HIV diagnosis was 17.8 years, and the median time was 17 years. Most (80%) of the patients were aged 50-64 years, and 20% were 65 and older.

The researchers collected sociodemographic, clinical, medication, and laboratory data for all patients at each clinical visit.

The mean number of non-ART medications was 6.7 for the population. Patients aged 65 years or older were taking significantly more non-ART medications than patients aged 50-64 (8.4 vs. 6.3; P < .001).

Similarly, those living with HIV for more than 10 years were taking significantly more non-ART medications (mean, 6.9) than those living with HIV for 10 or fewer years (mean 6.1; P = .0168).

In all, almost 60% of patients were taking at least one PIM. The mean number of PIMs per patient was 1.6.

Patients living with diagnosed HIV infection for more than 10 years were at greater risk of PIMs (1.6 PIMs) than those with shorter duration of HIV diagnosis (1.4 PIMs; P = .06).

Dr. McMillan says she hopes her study reminds clinicians to review patients’ medications at each visit and ensure they are neither over- nor underprescribing.

“From my perspective as a geriatrician, I hope that we do more dedicated medication reconciliation to actually make sure we know what people are taking,” she said. She asks patients to bring all their medications to the office so that they can review which ones match their diagnoses.

“I want to do more patient-centered personalized care for older adults, with a focus on people who are frail and who may have a limited life expectancy, so that we don’t have someone with a short life expectancy still taking 15 medications a day,” said Dr. McMillan.
 

‘Carefully document medications’

“This study identifies potentially inappropriate medication use in a group of older people living with HIV who are particularly vulnerable to it at an earlier age because of their medical complexity or frailty than perhaps healthy older adults,” Adrian Wagg, MD, professor of healthy aging in the department of medicine at the University of Alberta, Edmonton, told this news organization.

The study emphasizes the importance of careful documentation of medications that the patient is taking at every clinical visit, he said.

“Make sure you carefully document medications which are taken whenever you see the individual. Also try to limit the number of prescribers, because we know multiple prescribers are associated with greater likelihood of inappropriate prescribing,” Dr. Wagg said.

The move to wean patients from inappropriate medications is gaining momentum, he added.

“There is a huge movement now around actively deprescribing medications which are either no longer indicated or potentially of little benefit, given remaining life expectancy,” said Dr. Wagg. Drugs such as proton pump inhibitors, hypnotics, unrequired antidepressants, and benzodiazepines are the first targets for elimination, he concluded.

The study was funded by the University of Calgary. Dr. McMillan and Dr. Wagg reported no relevant financial relationships.

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

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

To the Editor:

A 52-year-old man who was otherwise healthy and a long-distance runner presented with the sudden onset of diminished sweating on the left side of the body of 6 weeks’ duration. While training for a marathon, he reported that he perspired only on the right side of the body during runs of 12 to 15 miles; he observed a lack of sweating on the left side of the face, left side of the trunk, left arm, and left leg. This absence of sweating was accompanied by intense flushing on the right side of the face and trunk.

The patient did not take any medications. He reported no history of trauma and exhibited no neurologic deficits. A chest radiograph was negative. Thyroid function testing and a comprehensive metabolic panel were normal. Contrast-enhanced computed tomography of the chest and abdomen revealed a 4.3-cm soft-tissue mass in the left superior mediastinum that was superior to the aortic arch, posterior to the left subclavian artery in proximity to the sympathetic chain, and lateral to the trachea. The patient was diagnosed with Harlequin syndrome (HS).

Open thoracotomy was performed to remove the lesion. Analysis of the mass showed cystic areas, areas of hemorrhage (Figure 1A), and alternating zones of compact Antoni A spindle cells admixed with areas of less orderly Antoni B spindle cells within a hypocellular stroma (Figure 1B). Individual cells were characterized by eosinophilic cytoplasm and tapered nuclei. The mass appeared to be completely encapsulated. No mitotic figures were seen on multiple slides. The cells stained diffusely positive for S-100 proteins. At 6-month follow-up, the patient reported that he did not notice any return of normal sweating on the left side. However, the right-sided flushing had resolved.

Harlequin syndrome (also called the Harlequin sign) is a rare disorder of the sympathetic nervous system and should not be confused with lethal harlequin-type ichthyosis, an autosomal-recessive congenital disorder in which the affected newborn’s skin is hard and thickened over most of the body.¹ Harlequin syndrome usually is characterized by unilateral flushing and sweating that can affect the face, trunk, and extremities.² Physical stimuli, such as exercising (as in our patient), high body temperature, and the consumption of spicy or pungent food, or an emotional response can unmask or exacerbate symptoms of HS. The syndrome also can present with cluster headache.³ Harlequin syndrome is more common in females (66% of cases).⁴ Originally, the side of the face marked by increased sweating and flushing was perceived to be the pathologic side; now it is recognized that the anhidrotic side is affected by the causative pathology. The side of the face characterized by flushing might gradually darken as it compensates for lack of thermal regulation on the other side.^2,5

Usually, HS is an idiopathic condition associated with localized failure of upper thoracic sympathetic chain ganglia.⁵ A theory is that HS is part of a spectrum of autoimmune autonomic ganglionopathy.⁶ Typically, the syndrome is asymptomatic at rest, but testing can reveal an underlying sympathetic lesion.⁷ Structural lesions have been reported as a cause of the syndrome,⁶ similar to our patient.

Disrupted thermoregulatory vasodilation in HS is caused by an ipsilateral lesion of the sympathetic vasodilator neurons that innervate the face. Hemifacial anhidrosis also occurs because sudomotor neurons travel within the same pathways as vasodilator neurons.⁴

Our patient had a posterior mediastinal ancient schwannoma to the left of the subclavian artery, lateral to the trachea, with ipsilateral anhidrosis of the forehead, cheek, chin, and torso. In the medical literature, the forehead, cheek, and chin are described as being affected in HS when the lesion is located under the bifurcation of the carotid artery.^3,5 Most of the sudomotor and vasomotor fibers that innervate the face leave the spinal cord through ventral roots T2-T3⁴ (symptomatic areas are described in Figure 2), which correlates with the hypothesis that HS results from a deficit originating in the third thoracic nerve that is caused by a peripheral lesion affecting sympathetic outflow through the third thoracic root.² The location of our patient’s lesion supports this claim.

Harlequin syndrome can present simultaneously with ipsilateral Horner, Adie, and Ross syndromes.⁸ There are varying clinical presentations of Horner syndrome. Some patients with HS show autonomic ocular signs, such as miosis and ptosis, exhibiting Horner syndrome as an additional feature.⁵ Adie syndrome is characterized by tonic pupils with hyporeflexia and is unilateral in most cases. Ross syndrome is similar to Adie syndrome—including tonic pupils with hyporeflexia—in addition to a finding of segmental anhidrosis; it is bilateral in most cases.⁴

In some cases, Horner syndrome and HS originate from unilateral pharmaceutical sympathetic denervation (ie, as a consequence of paravertebral spread of local anesthetic to ipsilateral stellate ganglion).⁹ Facial nonflushing areas in HS typically are identical with anhidrotic areas¹⁰; Horner syndrome often is ipsilateral to the affected sympathetic region.¹¹

Our patient exhibited secondary HS from a tumor effect; however, an underlying tumor or infarct is absent in many cases. In primary (idiopathic) cases of HS, treatment is not recommended because the syndrome is benign.^10,11

If symptoms of HS cause notable social embarrassment, contralateral sympathectomy can be considered.^5,12 Repeated stellate ganglion block with a local anesthetic could be a less invasive treatment option.¹³ When considered on a case-by-case-basis, botulinum toxin type A has been effective as a treatment of compensatory hyperhidrosis on the unaffected side.¹⁴

In cases of secondary HS, surgical removal of the lesion may alleviate symptoms, though thoracotomy in our patient to remove the schwannoma did not alleviate anhidrosis. The Table lists treatment options for primary and secondary HS.^4,5,11

Toddlers who watched more TV were significantly more likely than those who watched less TV to consume sugar-sweetened drinks and junk foods, based on data from 529 children.

Previous research had shown an association between screen time and poor diet, but most have involved school-aged children; the relationship in toddlers has not been well studied, Melissa R. Lutz, MD, of Johns Hopkins University, Baltimore, said in a presentation at the Pediatric Academic Societies annual meeting.

The American Academy of Pediatrics currently recommends no digital media for children younger than 18-24 months, and an hour or less daily for children aged 2-5 years.

To examine the association between TV time and dietary practices in 2-year-olds, the researchers conducted a secondary analysis of data from 529 children who presented for their 2-year-old well-child visit at a single center. The study population was 52% Latino/Hispanic and 30% non-Latino/Hispanic Black, and 69% had an annual household income less than $20,000. The median time spent watching TV daily was 42 minutes. The data were taken from participants in the Greenlight Intervention Study, a randomized trial of an obesity prevention program at four academic pediatric primary care clinics in the United States.

Daily screen time and dietary practices were based on parent reports, and included daily volume of juice, daily counts of fruits and vegetables, daily count of junk foods such as chips, ice cream, French fries, and fast food, and consumption of sugar-sweetened beverages. The cross-sectional analysis controlled for race/ethnicity, Women, Infants, and Children Program benefits, number of children at home, caregiver education level, and family income.

In adjusted analysis, more than an hour of TV time was significantly associated with junk food intake, with odds ratios of 1.12 for 90 minutes and 1.25 for 120 minutes (P < .05 for both). Similar associations were seen for TV times of 90 minutes and 120 minutes and intake of fast food and sugar-sweetened beverages.

Additionally, the researchers found that toddlers who watched TV during mealtimes were more than twice as likely to consume sugar-sweetened beverages (OR, 2.74), junk food (OR, 2.72), fast food (OR, 2.09), and only about half as likely to consume fruits and vegetables (OR, 0.62).

The study findings were limited by several factors including the cross-sectional design, the reliance on caregiver self-reports, potential for residual confounding, and the low average screen time, Dr. Lutz noted.

However, the results suggest that “increased screen TV time and mealtime TV were both associated with poor dietary practices in 2-year-old children,” she said.

Future research should include analysis of passive screen time, as well as the relationship between screen time and diet with other digital devices beyond TV, she added.
 

COVID drove screen time higher

The current study is especially important at this time because of the increased screen exposure for many young children in the wake of the ongoing pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview. “Screen time use is up even more than before [the pandemic], and this study is a reminder to ask parents of young children about screen time and dietary history.”

Dr. Kinsella said she was not surprised by the study findings. In her practice, “I see families with more screen time use in general who also are more likely to have juice and junk food available. If kids had no access to screens, I believe they would still have access to unhealthy foods. I believe more research is needed into why screen time is so high in some families.”

The study received funding from NIH. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Toddlers who watched more TV were significantly more likely than those who watched less TV to consume sugar-sweetened drinks and junk foods, based on data from 529 children.

Previous research had shown an association between screen time and poor diet, but most have involved school-aged children; the relationship in toddlers has not been well studied, Melissa R. Lutz, MD, of Johns Hopkins University, Baltimore, said in a presentation at the Pediatric Academic Societies annual meeting.

The American Academy of Pediatrics currently recommends no digital media for children younger than 18-24 months, and an hour or less daily for children aged 2-5 years.

To examine the association between TV time and dietary practices in 2-year-olds, the researchers conducted a secondary analysis of data from 529 children who presented for their 2-year-old well-child visit at a single center. The study population was 52% Latino/Hispanic and 30% non-Latino/Hispanic Black, and 69% had an annual household income less than $20,000. The median time spent watching TV daily was 42 minutes. The data were taken from participants in the Greenlight Intervention Study, a randomized trial of an obesity prevention program at four academic pediatric primary care clinics in the United States.

Daily screen time and dietary practices were based on parent reports, and included daily volume of juice, daily counts of fruits and vegetables, daily count of junk foods such as chips, ice cream, French fries, and fast food, and consumption of sugar-sweetened beverages. The cross-sectional analysis controlled for race/ethnicity, Women, Infants, and Children Program benefits, number of children at home, caregiver education level, and family income.

In adjusted analysis, more than an hour of TV time was significantly associated with junk food intake, with odds ratios of 1.12 for 90 minutes and 1.25 for 120 minutes (P < .05 for both). Similar associations were seen for TV times of 90 minutes and 120 minutes and intake of fast food and sugar-sweetened beverages.

Additionally, the researchers found that toddlers who watched TV during mealtimes were more than twice as likely to consume sugar-sweetened beverages (OR, 2.74), junk food (OR, 2.72), fast food (OR, 2.09), and only about half as likely to consume fruits and vegetables (OR, 0.62).

The study findings were limited by several factors including the cross-sectional design, the reliance on caregiver self-reports, potential for residual confounding, and the low average screen time, Dr. Lutz noted.

However, the results suggest that “increased screen TV time and mealtime TV were both associated with poor dietary practices in 2-year-old children,” she said.

Future research should include analysis of passive screen time, as well as the relationship between screen time and diet with other digital devices beyond TV, she added.
 

COVID drove screen time higher

The current study is especially important at this time because of the increased screen exposure for many young children in the wake of the ongoing pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview. “Screen time use is up even more than before [the pandemic], and this study is a reminder to ask parents of young children about screen time and dietary history.”

Dr. Kinsella said she was not surprised by the study findings. In her practice, “I see families with more screen time use in general who also are more likely to have juice and junk food available. If kids had no access to screens, I believe they would still have access to unhealthy foods. I believe more research is needed into why screen time is so high in some families.”

The study received funding from NIH. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Toddlers who watched more TV were significantly more likely than those who watched less TV to consume sugar-sweetened drinks and junk foods, based on data from 529 children.

Previous research had shown an association between screen time and poor diet, but most have involved school-aged children; the relationship in toddlers has not been well studied, Melissa R. Lutz, MD, of Johns Hopkins University, Baltimore, said in a presentation at the Pediatric Academic Societies annual meeting.

The American Academy of Pediatrics currently recommends no digital media for children younger than 18-24 months, and an hour or less daily for children aged 2-5 years.

To examine the association between TV time and dietary practices in 2-year-olds, the researchers conducted a secondary analysis of data from 529 children who presented for their 2-year-old well-child visit at a single center. The study population was 52% Latino/Hispanic and 30% non-Latino/Hispanic Black, and 69% had an annual household income less than $20,000. The median time spent watching TV daily was 42 minutes. The data were taken from participants in the Greenlight Intervention Study, a randomized trial of an obesity prevention program at four academic pediatric primary care clinics in the United States.

Daily screen time and dietary practices were based on parent reports, and included daily volume of juice, daily counts of fruits and vegetables, daily count of junk foods such as chips, ice cream, French fries, and fast food, and consumption of sugar-sweetened beverages. The cross-sectional analysis controlled for race/ethnicity, Women, Infants, and Children Program benefits, number of children at home, caregiver education level, and family income.

In adjusted analysis, more than an hour of TV time was significantly associated with junk food intake, with odds ratios of 1.12 for 90 minutes and 1.25 for 120 minutes (P < .05 for both). Similar associations were seen for TV times of 90 minutes and 120 minutes and intake of fast food and sugar-sweetened beverages.

Additionally, the researchers found that toddlers who watched TV during mealtimes were more than twice as likely to consume sugar-sweetened beverages (OR, 2.74), junk food (OR, 2.72), fast food (OR, 2.09), and only about half as likely to consume fruits and vegetables (OR, 0.62).

The study findings were limited by several factors including the cross-sectional design, the reliance on caregiver self-reports, potential for residual confounding, and the low average screen time, Dr. Lutz noted.

However, the results suggest that “increased screen TV time and mealtime TV were both associated with poor dietary practices in 2-year-old children,” she said.

Future research should include analysis of passive screen time, as well as the relationship between screen time and diet with other digital devices beyond TV, she added.
 

COVID drove screen time higher

The current study is especially important at this time because of the increased screen exposure for many young children in the wake of the ongoing pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview. “Screen time use is up even more than before [the pandemic], and this study is a reminder to ask parents of young children about screen time and dietary history.”

Dr. Kinsella said she was not surprised by the study findings. In her practice, “I see families with more screen time use in general who also are more likely to have juice and junk food available. If kids had no access to screens, I believe they would still have access to unhealthy foods. I believe more research is needed into why screen time is so high in some families.”

The study received funding from NIH. The researchers had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.

In 2021, the Food and Drug Administration approved 50 new drugs, but 24 will not be described here because they would probably not be used in pregnancy. The 24 are Aduhelm (aducanumab) to treat Alzheimer’s disease; Azstarys (serdexmethylphenidate and dexmethylphenidate), a combination CNS stimulant indicated for the treatment of ADHD; Cabenuva (cabotegravir and rilpivirine) to treat HIV; Voxzogo (vosoritide) for children with achondroplasia and open epiphyses; Qelbree (viloxazine) used in children aged 6-17 years to treat ADHD; and Pylarify (piflufolastat) for prostate cancer. Other anticancer drugs that will not be covered are Cosela (trilaciclib), Cytalux (pafolacianine), Exkivity (mobocertinib); Fotivda (tivozanib), Jemperli (dostarlimab-gxly), Lumakras (sotorasib), Pepaxto (melphalan flufenamide), Rybrevant (amivantamab-vmjw), Rylaze (asparaginase erwinia chrysanthemi), Scemblix (asciminib), Tepmetko (tepotinib), Tivdak (tisotumab vedotin-tftv), Truseltiq (infigratinib), Ukoniq (umbralisib), and Zynlonta (loncastuximab tesirine-lpyl).

Skytrofa (lonapegsomatropin-tcgd) will not be described below because it is indicated to treat short stature and is unlikely to be used in pregnancy. Nextstellis (drospirenone and estetrol) is used to prevent pregnancy.

Typically, for new drugs there will be no published reports describing their use in pregnant women. That information will come much later. In the sections below, the indications, effects on pregnant animals, and the potential for harm of a fetus/embryo are described. However, the relevance of animal data to human pregnancies is not great.

Adbry (tralokinumab) (molecular weight [MW], 147 kilodaltons), is indicated for the treatment of moderate to severe atopic dermatitis in adult patients whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. The drug did not harm fetal monkeys at doses that were 10 times the maximum recommended human dose.

Besremi (ropeginterferon alfa-2b-njft) (MW, 60 kDa) is an interferon alfa-2b indicated for the treatment of adults with polycythemia vera. It is given by subcutaneous injection every 2 weeks. Animal studies assessing reproductive toxicity have not been conducted. The manufacturer states that the drug may cause fetal harm and should be assumed to have abortifacient potential.

Brexafemme (ibrexafungerp) (MW, 922) is indicated for the treatment of vulvovaginal candidiasis. The drug was teratogenic in pregnant rabbits but not in pregnant rats. The manufacturer recommends females with reproductive potential should use effective contraception during treatment and for 4 days after the final dose.

Bylvay (odevixibat) (MW unknown) is indicated for the treatment of pruritus in patients aged 3 months and older. There are no human data regarding its use in pregnant women. The drug was teratogenic in pregnant rabbits. Although there are no data, the drug has low absorption following oral administration and breastfeeding is not expected to result in exposure of the infant.

Empaveli (pegcetacoplan) (MW, 44 kDa) is used to treat paroxysmal nocturnal hemoglobinuria. When the drug was given to pregnant cynomolgus monkeys there was an increase in abortions and stillbirths.

Evkeeza (evinacumab-dgnb) (MW, 146k) is used to treat homozygous familial hypercholesterolemia. The drug was teratogenic in rabbits but not rats.

Fexinidazole (MW not specified) is indicated to treat human African trypanosomiasis caused by the parasite Trypanosoma brucei gambiense. Additional information not available.

Kerendia (finerenone) (MW, 378), is indicated to reduce the risk of kidney and heart complications in chronic kidney disease associated with type 2 diabetes. The drug was teratogenic in rats.

Korsuva (difelikefalin) (MW, 679) is a kappa opioid–receptor agonist indicated for the treatment of moderate to severe pruritus associated with chronic kidney disease in adults undergoing hemodialysis. No adverse effects were observed in pregnant rats and rabbits. The limited human data on use of Korsuva in pregnant women are not sufficient to evaluate a drug associated risk for major birth defects or miscarriage.

Leqvio (inclisiran) (MW, 17,285) is indicated to treat heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease as an add-on therapy. The drug was not teratogenic in rats and rabbits.

Livmarli (maralixibat) (MW, 710) is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome. Because systemic absorption is low, the recommended clinical dose is not expected to result in measurable fetal exposure. No effects on fetal rats were observed.

Livtencity (maribavir) (MW, 376) is used to treat posttransplant cytomegalovirus infection that has not responded to other treatment. Embryo/fetal survival was reduced in rats but not in rabbits at doses less then the human dose.

Lupkynis (voclosporin) (MW, 1,215) is used to treat nephritis. Avoid use of Lupkynis in pregnant women because of the alcohol content of the drug formulation. The drug was embryocidal and feticidal in rats and rabbits but with no treatment-related fetal malformations or variations.

Lybalvi (olanzapine and samidorphan) (MW, 312 and 505) is a combination drug used to treat schizophrenia and bipolar disorder. It was fetal toxic in pregnant rats and rabbits but with no evidence of malformations. There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including this drug, during pregnancy. Health care providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or visit the Reproductive Psychiatry Resource and Information Center of the MGH Center for Women’s Mental Health.

Nexviazyme (avalglucosidase alfa-ngpt) (MW, 124k) is a hydrolytic lysosomal glycogen-specific enzyme indicated for the treatment of patients aged 1 year and older with late-onset Pompe disease. The drug was not teratogenic in mice and rabbits.

Nulibry (fosdenopterin) (MW, 480) is used to reduce the risk of mortality in molybdenum cofactor deficiency type A. Studies have not been conducted in pregnant animals.

Ponvory (ponesimod) (MW, 461) is used to treat relapsing forms of multiple sclerosis. The drug caused severe adverse effects in pregnant rats and rabbits.

Qulipta (atogepant) (MW, 604) is indicated to prevent episodic migraines. It is embryo/fetal toxic in rats and rabbits.

Saphnelo (anifrolumab-fnia) (MW, 148k) is used to treat moderate to severe systemic lupus erythematosus along with standard therapy. In pregnant cynomolgus monkeys, there was no evidence of embryotoxicity or fetal malformations with exposures up to approximately 28 times the exposure at the maximum recommended human dose.

Tavneos (avacopan) (MW, 582) is indicated to treat severe active antineutrophil cytoplasmic autoantibody–associated vasculitis in combination with standard therapy including glucocorticoids. There appears to be an increased risk for hepatotoxicity. The drug caused no defects in hamsters and rabbits, but in rabbits there was an increase in abortions.

Tezspire (tezepelumab-ekko) (MW, 147k) is indicated to treat severe asthma as an add-on maintenance therapy. No adverse fetal effects were observed in pregnant cynomolgus monkeys.

Verquvo (vericiguat) (MW, 426) is used to mitigate the risk of cardiovascular death and hospitalization for chronic heart failure. The drug was teratogenic in pregnant rabbits but not rats.

Vyvgart (efgartigimod alfa-fcab) (MW, 54k) is indicated to treat generalized myasthenia gravis. The drug did not cause birth defects in rats and rabbits.

Welireg (belzutifan) (MW, 383) is used to treat von Hippel–Lindau disease. In pregnant rats, the drug caused embryo-fetal lethality, reduced fetal body weight, and caused fetal skeletal malformations at maternal exposures of at least 0.2 times the human exposures.

Zegalogue (dasiglucagon) (MW, 3,382) is used to treat severe hypoglycemia. The drug did not cause birth defects in pregnant rats and rabbits.
 

Breastfeeding

It is not known if the above drugs will be in breast milk, but the safest course for an infant is to not breast feed if the mother is taking any of the above drugs.

Mr. Briggs is clinical professor of pharmacy at the University of California, San Francisco, and adjunct professor of pharmacy at the University of Southern California, Los Angeles, as well as at Washington State University, Spokane. Mr. Briggs said he had no relevant financial disclosures. Email him at obnews@mdedge.com.

One year after hospitalization for COVID-19 only a minority of people feel fully recovered, with being female, obesity, and having had mechanical ventilation in hospital risk factors for not feeling fully recovered.

In the new U.K. study of more than 2,000 patients, presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022), and published in The Lancet Respiratory Medicine, research showed that one in four patients feel fully well again 1 year after hospitalization for COVID-19.

For their study, researchers from the University of Leicester used data from the post-hospitalization COVID-19 (PHOSP-COVID) prospective, longitudinal cohort study, which assessed adults aged 18 years and over who had been hospitalized with COVID-19 across the United Kingdom and subsequently discharged. The researchers assessed the recovery of 2,320 participants discharged from 39 U.K. hospitals between March 7, 2020, and April 18, 2021, who were assessed via patient-reported outcome measures, physical performance, and organ function at 5 months and at 1 year after hospital discharge. Blood samples were taken at the 5-month visit to be analyzed for the presence of various inflammatory proteins.

All participants were assessed at 5 months after discharge and 807 participants (33%) completed both the 5-month and 1-year visits at the time of the analysis. The study is ongoing. The 807 patients were mean age of 59 years, 36% were women, and 28% received invasive mechanical ventilation. The proportion of patients reporting full recovery was similar between 5 months (26%) and 1 year (29%).
 

Female sex and obesity major risk factors for not recovering

Being female, obese, and having had mechanical ventilation in hospital makes someone 32%, 50%, and 58%, respectively, less likely to feel fully recovered 1 year after COVID-19 hospitalization, the authors said.

“We found female sex and obesity were major risk factors for not recovering at one year,” said the researchers, led by Rachael Evans, PhD, Louise V. Wain, and Christopher E. Brightling, PhD, National Institute for Health Research, Leicester Biomedical Research Centre, University of Leicester.

The authors said fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness were most common ongoing long COVID symptoms. They noted how the total number and range of ongoing symptoms at 1 year was “striking,” positively associated with the severity of long COVID, and emphasizes the “multisystem nature of long COVID.”
 

Several inflammatory mediators increased

An earlier publication from this study identified four groups or “clusters” of symptom severity at 5 months, which were confirmed by this new study at 1 year, the authors said. They reported that 20% had very severe physical and mental health impairment, 30% had severe physical and mental health impairment, 11% had moderate physical health impairment with cognitive impairment, and 39% had mild mental and physical health impairment.

They added that having obesity, reduced exercise capacity, a greater number of symptoms, and increased levels of C-reactive protein were associated with the “more severe clusters.” In both the very severe and the moderate with cognitive impairment clusters, levels of interleukin-6 (IL-6) were higher when compared with the mild cluster.

“The limited recovery from 5 months to 1 year after hospitalisation in our study across symptoms, mental health, exercise capacity, organ impairment, and quality-of-life is striking,” the researchers noted.

“In our clusters, female sex and obesity were also associated with more severe ongoing health impairments including reduced exercise performance and health-related quality of life at one year,” and suggested that this potentially highlighted a group that “might need higher intensity interventions such as supervised rehabilitation,” they added.

There are no specific therapeutics for long COVID, the researchers said, noting that “effective interventions are urgently required.” The persistent systemic inflammation identified, particularly in those in the very severe and moderate with cognitive impairment clusters, suggested that these groups “might respond to anti-inflammatory strategies,” the authors wrote.

“We found that a minority of participants felt fully recovered 1 year after hospital discharge, with minimal improvement after a 5-month assessment,” they noted.

They added that the findings suggest the need for complex interventions that target both physical and mental health impairments to alleviate symptoms, and that specific therapeutic approaches to manage posttraumatic stress disorder might also be needed. The authors pointed out how “pharmacological and non-pharmacological interventions are urgently needed,” with a “precision-medicine approach with potential treatable traits of systemic inflammation and obesity.”

They said their study highlighted the “urgent need for health-care services to support the large and rapidly increasing patient population in whom a substantial burden of symptoms exist, including reduced exercise capacity and substantially decreased health-related quality of life one year after hospital discharge.”

They warned that without effective treatments, long COVID could become a “highly prevalent new long-term condition.”

A version of this article first appeared on Medscape UK.

One year after hospitalization for COVID-19 only a minority of people feel fully recovered, with being female, obesity, and having had mechanical ventilation in hospital risk factors for not feeling fully recovered.

In the new U.K. study of more than 2,000 patients, presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022), and published in The Lancet Respiratory Medicine, research showed that one in four patients feel fully well again 1 year after hospitalization for COVID-19.

For their study, researchers from the University of Leicester used data from the post-hospitalization COVID-19 (PHOSP-COVID) prospective, longitudinal cohort study, which assessed adults aged 18 years and over who had been hospitalized with COVID-19 across the United Kingdom and subsequently discharged. The researchers assessed the recovery of 2,320 participants discharged from 39 U.K. hospitals between March 7, 2020, and April 18, 2021, who were assessed via patient-reported outcome measures, physical performance, and organ function at 5 months and at 1 year after hospital discharge. Blood samples were taken at the 5-month visit to be analyzed for the presence of various inflammatory proteins.

All participants were assessed at 5 months after discharge and 807 participants (33%) completed both the 5-month and 1-year visits at the time of the analysis. The study is ongoing. The 807 patients were mean age of 59 years, 36% were women, and 28% received invasive mechanical ventilation. The proportion of patients reporting full recovery was similar between 5 months (26%) and 1 year (29%).
 

Female sex and obesity major risk factors for not recovering

Being female, obese, and having had mechanical ventilation in hospital makes someone 32%, 50%, and 58%, respectively, less likely to feel fully recovered 1 year after COVID-19 hospitalization, the authors said.

“We found female sex and obesity were major risk factors for not recovering at one year,” said the researchers, led by Rachael Evans, PhD, Louise V. Wain, and Christopher E. Brightling, PhD, National Institute for Health Research, Leicester Biomedical Research Centre, University of Leicester.

The authors said fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness were most common ongoing long COVID symptoms. They noted how the total number and range of ongoing symptoms at 1 year was “striking,” positively associated with the severity of long COVID, and emphasizes the “multisystem nature of long COVID.”
 

Several inflammatory mediators increased

An earlier publication from this study identified four groups or “clusters” of symptom severity at 5 months, which were confirmed by this new study at 1 year, the authors said. They reported that 20% had very severe physical and mental health impairment, 30% had severe physical and mental health impairment, 11% had moderate physical health impairment with cognitive impairment, and 39% had mild mental and physical health impairment.

They added that having obesity, reduced exercise capacity, a greater number of symptoms, and increased levels of C-reactive protein were associated with the “more severe clusters.” In both the very severe and the moderate with cognitive impairment clusters, levels of interleukin-6 (IL-6) were higher when compared with the mild cluster.

“The limited recovery from 5 months to 1 year after hospitalisation in our study across symptoms, mental health, exercise capacity, organ impairment, and quality-of-life is striking,” the researchers noted.

“In our clusters, female sex and obesity were also associated with more severe ongoing health impairments including reduced exercise performance and health-related quality of life at one year,” and suggested that this potentially highlighted a group that “might need higher intensity interventions such as supervised rehabilitation,” they added.

There are no specific therapeutics for long COVID, the researchers said, noting that “effective interventions are urgently required.” The persistent systemic inflammation identified, particularly in those in the very severe and moderate with cognitive impairment clusters, suggested that these groups “might respond to anti-inflammatory strategies,” the authors wrote.

“We found that a minority of participants felt fully recovered 1 year after hospital discharge, with minimal improvement after a 5-month assessment,” they noted.

They added that the findings suggest the need for complex interventions that target both physical and mental health impairments to alleviate symptoms, and that specific therapeutic approaches to manage posttraumatic stress disorder might also be needed. The authors pointed out how “pharmacological and non-pharmacological interventions are urgently needed,” with a “precision-medicine approach with potential treatable traits of systemic inflammation and obesity.”

They said their study highlighted the “urgent need for health-care services to support the large and rapidly increasing patient population in whom a substantial burden of symptoms exist, including reduced exercise capacity and substantially decreased health-related quality of life one year after hospital discharge.”

They warned that without effective treatments, long COVID could become a “highly prevalent new long-term condition.”

A version of this article first appeared on Medscape UK.

One year after hospitalization for COVID-19 only a minority of people feel fully recovered, with being female, obesity, and having had mechanical ventilation in hospital risk factors for not feeling fully recovered.

In the new U.K. study of more than 2,000 patients, presented at this year’s European Congress of Clinical Microbiology & Infectious Diseases (ECCMID 2022), and published in The Lancet Respiratory Medicine, research showed that one in four patients feel fully well again 1 year after hospitalization for COVID-19.

For their study, researchers from the University of Leicester used data from the post-hospitalization COVID-19 (PHOSP-COVID) prospective, longitudinal cohort study, which assessed adults aged 18 years and over who had been hospitalized with COVID-19 across the United Kingdom and subsequently discharged. The researchers assessed the recovery of 2,320 participants discharged from 39 U.K. hospitals between March 7, 2020, and April 18, 2021, who were assessed via patient-reported outcome measures, physical performance, and organ function at 5 months and at 1 year after hospital discharge. Blood samples were taken at the 5-month visit to be analyzed for the presence of various inflammatory proteins.

All participants were assessed at 5 months after discharge and 807 participants (33%) completed both the 5-month and 1-year visits at the time of the analysis. The study is ongoing. The 807 patients were mean age of 59 years, 36% were women, and 28% received invasive mechanical ventilation. The proportion of patients reporting full recovery was similar between 5 months (26%) and 1 year (29%).
 

Female sex and obesity major risk factors for not recovering

Being female, obese, and having had mechanical ventilation in hospital makes someone 32%, 50%, and 58%, respectively, less likely to feel fully recovered 1 year after COVID-19 hospitalization, the authors said.

“We found female sex and obesity were major risk factors for not recovering at one year,” said the researchers, led by Rachael Evans, PhD, Louise V. Wain, and Christopher E. Brightling, PhD, National Institute for Health Research, Leicester Biomedical Research Centre, University of Leicester.

The authors said fatigue, muscle pain, physically slowing down, poor sleep, and breathlessness were most common ongoing long COVID symptoms. They noted how the total number and range of ongoing symptoms at 1 year was “striking,” positively associated with the severity of long COVID, and emphasizes the “multisystem nature of long COVID.”
 

Several inflammatory mediators increased

An earlier publication from this study identified four groups or “clusters” of symptom severity at 5 months, which were confirmed by this new study at 1 year, the authors said. They reported that 20% had very severe physical and mental health impairment, 30% had severe physical and mental health impairment, 11% had moderate physical health impairment with cognitive impairment, and 39% had mild mental and physical health impairment.

They added that having obesity, reduced exercise capacity, a greater number of symptoms, and increased levels of C-reactive protein were associated with the “more severe clusters.” In both the very severe and the moderate with cognitive impairment clusters, levels of interleukin-6 (IL-6) were higher when compared with the mild cluster.

“The limited recovery from 5 months to 1 year after hospitalisation in our study across symptoms, mental health, exercise capacity, organ impairment, and quality-of-life is striking,” the researchers noted.

“In our clusters, female sex and obesity were also associated with more severe ongoing health impairments including reduced exercise performance and health-related quality of life at one year,” and suggested that this potentially highlighted a group that “might need higher intensity interventions such as supervised rehabilitation,” they added.

There are no specific therapeutics for long COVID, the researchers said, noting that “effective interventions are urgently required.” The persistent systemic inflammation identified, particularly in those in the very severe and moderate with cognitive impairment clusters, suggested that these groups “might respond to anti-inflammatory strategies,” the authors wrote.

“We found that a minority of participants felt fully recovered 1 year after hospital discharge, with minimal improvement after a 5-month assessment,” they noted.

They added that the findings suggest the need for complex interventions that target both physical and mental health impairments to alleviate symptoms, and that specific therapeutic approaches to manage posttraumatic stress disorder might also be needed. The authors pointed out how “pharmacological and non-pharmacological interventions are urgently needed,” with a “precision-medicine approach with potential treatable traits of systemic inflammation and obesity.”

They said their study highlighted the “urgent need for health-care services to support the large and rapidly increasing patient population in whom a substantial burden of symptoms exist, including reduced exercise capacity and substantially decreased health-related quality of life one year after hospital discharge.”

They warned that without effective treatments, long COVID could become a “highly prevalent new long-term condition.”

A version of this article first appeared on Medscape UK.

Climate-informed clinical encounters have the potential to enhance pediatric care in a variety of ways, according to Aaron Bernstein, MD, of Boston Children’s Hospital.

“Each primary care visit offers opportunities to screen for and support children burdened with risks to health that are increasingly intense due to climate change,” Rebecca P. Philipsborn, MD, of Emory University, Atlanta, and colleagues wrote in “A pediatrician’s guide to climate change–informed primary care,” on which Dr. Bernstein served as corresponding author (Curr Probl Pediatr Adolesc Health Care. 2021 June. doi: 10.1016/j.cppeds.2021.101027).

In a presentation at the annual meeting of the Pediatric Academic Societies, Dr. Bernstein highlighted five components of climate-informed pediatric care mentioned in the article: climate-informed screening, health promotion that includes health and climate benefits, care management that anticipates climate risks for at-risk children, climate-informed anticipatory guidance, and engagement with community resources and advocacy.

Pediatricians can incorporate climate-related issues into screening protocols by asking patients about their home environment, Dr. Bernstein said. Potential questions to ask include whether the family has air conditioning in the home, and whether they are concerned about being able to pay the bill if they use air conditioning, he said.

Health promotion discussions during clinical encounters can emphasize that eating more fruits and vegetables not only is good for the health of the child and the whole family, but “also is good for the planet we live on,” he said.

Care management strategies should anticipate climate risks for at-risk children, such those with complex or chronic medical conditions, and outdoor athletes for whom air quality might be an issue, he said.

Medication management has a climate-informed aspect, Dr. Bernstein said. “How safe are the medications you prescribe?” he asked. During the summer months, the relative risk of hospitalization with heat exposure is increased for a range of drugs including ACE inhibitors (RR 1.42), loop diuretics (RR 1.52), stimulants (RR 1.53), anticholinergics (RR 1.26), antipsychotics (RR 1.51), and beta-blockers (RR 1.08), he noted.

For children who play outdoor sports, previous studies suggest they acclimatize for approximately 7 days if traveling prior to vigorous exercise outdoors. “Monitor the heat index and limit the intensity or length of exercise on extreme heat index days,” Dr. Bernstein said. He emphasized the need to remind children and parents to try to limit intense physical activity to the coolest parts of the day, before 10 a.m. and after 4 p.m., to wear sunscreen and light-colored, lightweight clothing, and to drink 5-8 ounces of fluid every 20 minutes during exercise.

Approximately 12% of all-cause attributable fractions of emergency department visits are associated with heat exposure, Dr. Bernstein added. He recommended that pediatricians and patients be aware of airnow.gov and iqair.com as resources to monitor air quality. Pay attention to the heat index, which factors in humidity and presents the real-feel temperature, not just the thermometer reading.

Last but not least, Dr. Bernstein explained that pediatricians can use a clinical visit to ask adolescent patients about civic engagement, and offer resources for those who want to learn more about climate change, such as climatechangeresources.org/organizations-kids/.

For more detailed guidance, Dr. Bernstein recommended “A pediatrician’s guide to climate change–informed primary care.”

Use websites and handouts

Including climate issues in pediatric visits is definitely important, Suzanne Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview.

“Some questions are more critical in warm weather environments where children are at higher risk for dehydration and heat exposure,” said Dr. Boulter, who was not involved with the guide preparation. “The list of suggestions for participation in outdoor sports in hot weather is comprehensive, and the data on ER visits in summer months is surprising,” she noted. However, some of the data could have included more explanation, such as what air quality actually measures, and the difference between ambient temperature and heat index, and how they are calculated, she noted.

Questions about diet, air conditioning, and backup power sources may be covered in other areas of the pediatric visit, or on questionnaires prior to the visit, Dr. Boulter added.

The main barrier to incorporating climate-related information during the pediatric visit is the limited time allotted for the visit and number of topics to address, said Dr. Boulter. “Pediatric practices that have websites could post seasonal reminders about sports participation health in hot weather, or have printed brief handouts for patients in the office,” she noted. Alternatively, guidance about sports and the impact of climate could easily be given as a short handout to families during the health visit, she said.

Future research might include a focus on assessing families’ knowledge and behavior before and after climate change counseling, Dr. Boulter added.

Dr. Bernstein and Dr. Boulter had no financial conflicts to disclose. Dr. Boulter serves on the editorial advisory board of Pediatric News.

Climate-informed clinical encounters have the potential to enhance pediatric care in a variety of ways, according to Aaron Bernstein, MD, of Boston Children’s Hospital.

“Each primary care visit offers opportunities to screen for and support children burdened with risks to health that are increasingly intense due to climate change,” Rebecca P. Philipsborn, MD, of Emory University, Atlanta, and colleagues wrote in “A pediatrician’s guide to climate change–informed primary care,” on which Dr. Bernstein served as corresponding author (Curr Probl Pediatr Adolesc Health Care. 2021 June. doi: 10.1016/j.cppeds.2021.101027).

In a presentation at the annual meeting of the Pediatric Academic Societies, Dr. Bernstein highlighted five components of climate-informed pediatric care mentioned in the article: climate-informed screening, health promotion that includes health and climate benefits, care management that anticipates climate risks for at-risk children, climate-informed anticipatory guidance, and engagement with community resources and advocacy.

Pediatricians can incorporate climate-related issues into screening protocols by asking patients about their home environment, Dr. Bernstein said. Potential questions to ask include whether the family has air conditioning in the home, and whether they are concerned about being able to pay the bill if they use air conditioning, he said.

Health promotion discussions during clinical encounters can emphasize that eating more fruits and vegetables not only is good for the health of the child and the whole family, but “also is good for the planet we live on,” he said.

Care management strategies should anticipate climate risks for at-risk children, such those with complex or chronic medical conditions, and outdoor athletes for whom air quality might be an issue, he said.

Medication management has a climate-informed aspect, Dr. Bernstein said. “How safe are the medications you prescribe?” he asked. During the summer months, the relative risk of hospitalization with heat exposure is increased for a range of drugs including ACE inhibitors (RR 1.42), loop diuretics (RR 1.52), stimulants (RR 1.53), anticholinergics (RR 1.26), antipsychotics (RR 1.51), and beta-blockers (RR 1.08), he noted.

For children who play outdoor sports, previous studies suggest they acclimatize for approximately 7 days if traveling prior to vigorous exercise outdoors. “Monitor the heat index and limit the intensity or length of exercise on extreme heat index days,” Dr. Bernstein said. He emphasized the need to remind children and parents to try to limit intense physical activity to the coolest parts of the day, before 10 a.m. and after 4 p.m., to wear sunscreen and light-colored, lightweight clothing, and to drink 5-8 ounces of fluid every 20 minutes during exercise.

Approximately 12% of all-cause attributable fractions of emergency department visits are associated with heat exposure, Dr. Bernstein added. He recommended that pediatricians and patients be aware of airnow.gov and iqair.com as resources to monitor air quality. Pay attention to the heat index, which factors in humidity and presents the real-feel temperature, not just the thermometer reading.

Last but not least, Dr. Bernstein explained that pediatricians can use a clinical visit to ask adolescent patients about civic engagement, and offer resources for those who want to learn more about climate change, such as climatechangeresources.org/organizations-kids/.

For more detailed guidance, Dr. Bernstein recommended “A pediatrician’s guide to climate change–informed primary care.”

Use websites and handouts

Including climate issues in pediatric visits is definitely important, Suzanne Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview.

“Some questions are more critical in warm weather environments where children are at higher risk for dehydration and heat exposure,” said Dr. Boulter, who was not involved with the guide preparation. “The list of suggestions for participation in outdoor sports in hot weather is comprehensive, and the data on ER visits in summer months is surprising,” she noted. However, some of the data could have included more explanation, such as what air quality actually measures, and the difference between ambient temperature and heat index, and how they are calculated, she noted.

Questions about diet, air conditioning, and backup power sources may be covered in other areas of the pediatric visit, or on questionnaires prior to the visit, Dr. Boulter added.

The main barrier to incorporating climate-related information during the pediatric visit is the limited time allotted for the visit and number of topics to address, said Dr. Boulter. “Pediatric practices that have websites could post seasonal reminders about sports participation health in hot weather, or have printed brief handouts for patients in the office,” she noted. Alternatively, guidance about sports and the impact of climate could easily be given as a short handout to families during the health visit, she said.

Future research might include a focus on assessing families’ knowledge and behavior before and after climate change counseling, Dr. Boulter added.

Dr. Bernstein and Dr. Boulter had no financial conflicts to disclose. Dr. Boulter serves on the editorial advisory board of Pediatric News.

Climate-informed clinical encounters have the potential to enhance pediatric care in a variety of ways, according to Aaron Bernstein, MD, of Boston Children’s Hospital.

“Each primary care visit offers opportunities to screen for and support children burdened with risks to health that are increasingly intense due to climate change,” Rebecca P. Philipsborn, MD, of Emory University, Atlanta, and colleagues wrote in “A pediatrician’s guide to climate change–informed primary care,” on which Dr. Bernstein served as corresponding author (Curr Probl Pediatr Adolesc Health Care. 2021 June. doi: 10.1016/j.cppeds.2021.101027).

In a presentation at the annual meeting of the Pediatric Academic Societies, Dr. Bernstein highlighted five components of climate-informed pediatric care mentioned in the article: climate-informed screening, health promotion that includes health and climate benefits, care management that anticipates climate risks for at-risk children, climate-informed anticipatory guidance, and engagement with community resources and advocacy.

Pediatricians can incorporate climate-related issues into screening protocols by asking patients about their home environment, Dr. Bernstein said. Potential questions to ask include whether the family has air conditioning in the home, and whether they are concerned about being able to pay the bill if they use air conditioning, he said.

Health promotion discussions during clinical encounters can emphasize that eating more fruits and vegetables not only is good for the health of the child and the whole family, but “also is good for the planet we live on,” he said.

Care management strategies should anticipate climate risks for at-risk children, such those with complex or chronic medical conditions, and outdoor athletes for whom air quality might be an issue, he said.

Medication management has a climate-informed aspect, Dr. Bernstein said. “How safe are the medications you prescribe?” he asked. During the summer months, the relative risk of hospitalization with heat exposure is increased for a range of drugs including ACE inhibitors (RR 1.42), loop diuretics (RR 1.52), stimulants (RR 1.53), anticholinergics (RR 1.26), antipsychotics (RR 1.51), and beta-blockers (RR 1.08), he noted.

For children who play outdoor sports, previous studies suggest they acclimatize for approximately 7 days if traveling prior to vigorous exercise outdoors. “Monitor the heat index and limit the intensity or length of exercise on extreme heat index days,” Dr. Bernstein said. He emphasized the need to remind children and parents to try to limit intense physical activity to the coolest parts of the day, before 10 a.m. and after 4 p.m., to wear sunscreen and light-colored, lightweight clothing, and to drink 5-8 ounces of fluid every 20 minutes during exercise.

Approximately 12% of all-cause attributable fractions of emergency department visits are associated with heat exposure, Dr. Bernstein added. He recommended that pediatricians and patients be aware of airnow.gov and iqair.com as resources to monitor air quality. Pay attention to the heat index, which factors in humidity and presents the real-feel temperature, not just the thermometer reading.

Last but not least, Dr. Bernstein explained that pediatricians can use a clinical visit to ask adolescent patients about civic engagement, and offer resources for those who want to learn more about climate change, such as climatechangeresources.org/organizations-kids/.

For more detailed guidance, Dr. Bernstein recommended “A pediatrician’s guide to climate change–informed primary care.”

Use websites and handouts

Including climate issues in pediatric visits is definitely important, Suzanne Boulter, MD, of the Geisel School of Medicine at Dartmouth, Hanover, N.H., said in an interview.

“Some questions are more critical in warm weather environments where children are at higher risk for dehydration and heat exposure,” said Dr. Boulter, who was not involved with the guide preparation. “The list of suggestions for participation in outdoor sports in hot weather is comprehensive, and the data on ER visits in summer months is surprising,” she noted. However, some of the data could have included more explanation, such as what air quality actually measures, and the difference between ambient temperature and heat index, and how they are calculated, she noted.

Questions about diet, air conditioning, and backup power sources may be covered in other areas of the pediatric visit, or on questionnaires prior to the visit, Dr. Boulter added.

The main barrier to incorporating climate-related information during the pediatric visit is the limited time allotted for the visit and number of topics to address, said Dr. Boulter. “Pediatric practices that have websites could post seasonal reminders about sports participation health in hot weather, or have printed brief handouts for patients in the office,” she noted. Alternatively, guidance about sports and the impact of climate could easily be given as a short handout to families during the health visit, she said.

Future research might include a focus on assessing families’ knowledge and behavior before and after climate change counseling, Dr. Boulter added.

Dr. Bernstein and Dr. Boulter had no financial conflicts to disclose. Dr. Boulter serves on the editorial advisory board of Pediatric News.

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

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

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

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

Testing the DNA of antimicrobial-resistant Plasmodium falciparum in the blood of travelers from malaria-endemic regions may help researchers monitor how drug resistance changes over time, a study from Canada reports.

“Malaria remains the deadliest vector-borne infectious disease worldwide. Plasmodium spp., most commonly P. falciparum, are responsible for [approximately] 229 million cases and 500,000 deaths from malaria annually,” the authors write in Emerging Infectious Diseases.

“Our findings demonstrate an absence of genetic markers of resistance to the most powerful antimalarials on the planet – the artemisinins – in potentially deadly malaria imported primarily from sub-Saharan Africa over time. This is good news,” senior study author Andrea K. Boggild, MD, MSc, DTMH, told this news organization.

“We also showed that over 90% of falciparum malaria imports were resistant to the proguanil component of the fixed drug combination atovaquone-proguanil, a popular oral antimalarial that is first-line treatment for uncomplicated malaria in Canada,” Dr. Boggild, an associate professor in the department of medicine at the University of Toronto, Canada, added in an email. “We documented no genetic markers of atovaquone resistance.”
 

Search for global patterns of emerging drug resistance

Dr. Boggild, the medical director of the tropical disease unit at Toronto General Hospital, and colleagues analyzed 243 whole-blood specimens that contained P. falciparum and no other Plasmodium species from the malaria biobank at the Public Health Ontario Laboratory in Toronto. They analyzed specimens from the years 2008-2009, 2013-2014, and 2017-2018 from patients ranging in age from 3 to 88 years. Of the 186 patients with a documented travel history, 81 had traveled in West Africa, the most common region, and 40 in Nigeria, the most common country. Five specimens came from travelers to Southeast Asia, and one came from a traveler to the Caribbean.

The researchers extracted DNA from whole blood and detected the parasite’s DNA by real-time quantitative polymerase chain reaction (qPCR). They analyzed 23 different single-nucleotide polymorphisms (SNPs) in six genes, and quantified the prevalence of resistance markers, including genes that provoke resistance to the most common antimalarial drugs: chloroquine, mefloquine, atovaquone/proguanil, and the artemisinins.

They analyzed SNPs at atpase6 (pfATPase6), pfcrt (chloroquine resistance transporter, cytb (cytochrome b), dhfr (dihydrofolate reductase), dhps (dihydropteroate synthetase), mdr1 (multidrug resistance protein) and mdr1 copy number, and kelch13 (kelch protein gene on chromosome 13).

Over time, they detected increasing mutant genotypes for dhfr S108N (P = .001) and dhps A613T (P = .029) but decreasing mutant genotypes for mdr1 N86Y (P < .001), D1246Y (P = .003), pfcrt K76T (P = .011), and pfcrt 74-75 (P = .014). They found no kelch13 mutations. They detected fewer mutations indicating chloroquine resistance over time, suggesting less chloroquine pressure in specimens from travelers to Africa, but mutations that provided proguanil resistance increased.

“Antimalarial resistance – particularly resistance to the powerful artemisinins – continues to expand globally, and it is important to conduct routine surveillance for resistant parasites in order to inform appropriate prevention and treatment guidelines,” Dr. Boggild explained. “It cannot be presumed that a drug’s efficacy will be durable over time given the global landscape of antimalarial resistance.”

Dr. Boggild acknowledged limitations to the study, including incomplete travel history in about half of the patients, relatively few patients from Southeast Asia, and the small sample set.

“Clinicians caring for travelers before or after travel should familiarize themselves with the options for malaria prevention and treatment and understand the risk–benefit profile of each drug,” Dr. Boggild advised. 

“Resistance to proguanil means that we are reliant on the partner drug atovaquone for the antimalarial action of this formulation, which is effective only when taken with food,” she added.

Anne N. Cowell, MD, MPH, of the division of infectious diseases at the University of California, San Diego, was not surprised by the findings.

“The study demonstrates how quickly malaria parasites adapt and evolve to survive changes in malaria treatment,” Dr. Cowell, who was not involved in the study, told this news organization.

“These changes reflect changing malaria treatment and thus drug pressure during the time period,” she said in an email. “Because the majority of the clinical samples with a known travel history came from West Africa, and there was no clear evidence of artemisinin resistance in the area during the final time period studied, it is not surprising that they did not find kelch13 resistance mutations.

“The increase in mutations associated with proguanil resistance is concerning because atovaquone-proguanil is frequently used for prophylaxis during travel,” Dr. Cowell added. “There is no widespread evidence of resistance in travelers at this time, but it warrants monitoring.”

Sean C. Murphy, MD, PhD, an associate professor of laboratory medicine and the director of the malaria molecular diagnostic laboratory at the University of Washington in Seattle, also was not surprised by the study’s results.

“It may be just a matter of time before evidence of artemisinin resistance crops up among returning travelers,” he said in an email. “When that happens, we may lose the opportunity to easily use common go-to drugs like atovaquone/proguanil to treat these patients.

“The biggest takeaway of this study is the reminder that drug-resistant malaria (including the future potential for artemisinin-resistant malaria) is just an airplane flight or two away from nonendemic places like Canada and the United States,” Dr. Murphy noted. He was not involved with this Canadian study.

“Continued investment is needed to support malaria control, drug resistance monitoring, and vaccine efforts in order to fight this relentless, terrible parasite,” he urged.

The Project Initiation Fund of Public Health Ontario funded the study. The study authors, Dr. Cowell, and Dr. Murphy have disclosed no relevant financial relationships.  

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

Political elections can be hard on the heart, suggests a study that showed a substantial uptick in hospital admissions for acute cardiovascular conditions immediately after the 2020 American presidential election.

The analysis of nearly 6.4 million adults showed that the rate of hospitalization for acute cardiovascular disease (CVD) was 17% higher in the 5 days after the election than in a 5-day period 2 weeks earlier.

The rate of acute myocardial infarction (AMI) was 42% higher, with no significant difference for heart failure or stroke hospital admissions.

“These findings suggest that awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed,” write Matthew T. Mefford, PhD, of Kaiser Permanente Southern California, Pasadena, and colleagues.

The study was published in the April issue of JAMA Network Open.
 

Stress and the heart

In the American Psychological Association Stress in America 2020 survey conducted roughly 3 months before the 2020 presidential election, 77% of adults cited the future of the country as a substantial source of stress, enhanced by the ongoing COVID-19 pandemic, the authors note. More than two-thirds said the election was a substantial source of stress.

Dr. Mefford and colleagues compared CVD hospitalizations at Kaiser Permanente Southern and Northern California hospitals in the 5-day risk window of Nov. 4-8, 2020, with the control window of Oct. 21-25, 2020.

There were 666 CVD hospitalizations (760.47 per 100,000 person-years [PY]) in the risk window, compared with 569 (647.97 per 100,000 PY) in the control window (rate ratio, 1.17; 95% confidence interval, 1.05-1.31).

There were also significantly more hospitalizations for AMI immediately after the election than before (179 vs. 126 AMI hospitalizations; 204.4 vs. 143.5 per 100,000 PY; RR, 1.42; 95% CI, 1.13-1.79).

There was no significant difference between the risk and control periods for hospitalizations because of stroke or heart failure.

The study also suggests higher rates of acute CVD after the election in older adults, men, and White individuals. Political affiliation was not examined in the study.

“Importantly, results were consistent before and after excluding patients with confirmed COVID-19 infection,” the study team notes.

Yet, the potential influence of COVID-19 stressors on increasing CVD risk cannot be ruled out, they say.

However, COVID-19 stressors occurred over a much longer period and are less likely to explain the transient risks observed in the defined risk and control windows that are in close proximity to the 2020 election, the investigators point out.

There is growing evidence that psychological health contributes to CVD.

Previous studies shown a higher risk for acute CVD around population-wide psychosocial or environmental stressors, but less was known about acute CVD risk in relation to political events.

The researchers note future studies evaluating stress-relieving interventions may be important for understanding the intersection of political events, associated stress, and acute CVD risk.

Partial funding for the study was provided by a grant from the W.K. Kellogg Foundation. The authors have no relevant conflicts of interest.

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

Political elections can be hard on the heart, suggests a study that showed a substantial uptick in hospital admissions for acute cardiovascular conditions immediately after the 2020 American presidential election.

The analysis of nearly 6.4 million adults showed that the rate of hospitalization for acute cardiovascular disease (CVD) was 17% higher in the 5 days after the election than in a 5-day period 2 weeks earlier.

The rate of acute myocardial infarction (AMI) was 42% higher, with no significant difference for heart failure or stroke hospital admissions.

“These findings suggest that awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed,” write Matthew T. Mefford, PhD, of Kaiser Permanente Southern California, Pasadena, and colleagues.

The study was published in the April issue of JAMA Network Open.
 

Stress and the heart

In the American Psychological Association Stress in America 2020 survey conducted roughly 3 months before the 2020 presidential election, 77% of adults cited the future of the country as a substantial source of stress, enhanced by the ongoing COVID-19 pandemic, the authors note. More than two-thirds said the election was a substantial source of stress.

Dr. Mefford and colleagues compared CVD hospitalizations at Kaiser Permanente Southern and Northern California hospitals in the 5-day risk window of Nov. 4-8, 2020, with the control window of Oct. 21-25, 2020.

There were 666 CVD hospitalizations (760.47 per 100,000 person-years [PY]) in the risk window, compared with 569 (647.97 per 100,000 PY) in the control window (rate ratio, 1.17; 95% confidence interval, 1.05-1.31).

There were also significantly more hospitalizations for AMI immediately after the election than before (179 vs. 126 AMI hospitalizations; 204.4 vs. 143.5 per 100,000 PY; RR, 1.42; 95% CI, 1.13-1.79).

There was no significant difference between the risk and control periods for hospitalizations because of stroke or heart failure.

The study also suggests higher rates of acute CVD after the election in older adults, men, and White individuals. Political affiliation was not examined in the study.

“Importantly, results were consistent before and after excluding patients with confirmed COVID-19 infection,” the study team notes.

Yet, the potential influence of COVID-19 stressors on increasing CVD risk cannot be ruled out, they say.

However, COVID-19 stressors occurred over a much longer period and are less likely to explain the transient risks observed in the defined risk and control windows that are in close proximity to the 2020 election, the investigators point out.

There is growing evidence that psychological health contributes to CVD.

Previous studies shown a higher risk for acute CVD around population-wide psychosocial or environmental stressors, but less was known about acute CVD risk in relation to political events.

The researchers note future studies evaluating stress-relieving interventions may be important for understanding the intersection of political events, associated stress, and acute CVD risk.

Partial funding for the study was provided by a grant from the W.K. Kellogg Foundation. The authors have no relevant conflicts of interest.

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

Political elections can be hard on the heart, suggests a study that showed a substantial uptick in hospital admissions for acute cardiovascular conditions immediately after the 2020 American presidential election.

The analysis of nearly 6.4 million adults showed that the rate of hospitalization for acute cardiovascular disease (CVD) was 17% higher in the 5 days after the election than in a 5-day period 2 weeks earlier.

The rate of acute myocardial infarction (AMI) was 42% higher, with no significant difference for heart failure or stroke hospital admissions.

“These findings suggest that awareness of the heightened risk of CVD and strategies to mitigate risk during notable political events are needed,” write Matthew T. Mefford, PhD, of Kaiser Permanente Southern California, Pasadena, and colleagues.

The study was published in the April issue of JAMA Network Open.
 

Stress and the heart

In the American Psychological Association Stress in America 2020 survey conducted roughly 3 months before the 2020 presidential election, 77% of adults cited the future of the country as a substantial source of stress, enhanced by the ongoing COVID-19 pandemic, the authors note. More than two-thirds said the election was a substantial source of stress.

Dr. Mefford and colleagues compared CVD hospitalizations at Kaiser Permanente Southern and Northern California hospitals in the 5-day risk window of Nov. 4-8, 2020, with the control window of Oct. 21-25, 2020.

There were 666 CVD hospitalizations (760.47 per 100,000 person-years [PY]) in the risk window, compared with 569 (647.97 per 100,000 PY) in the control window (rate ratio, 1.17; 95% confidence interval, 1.05-1.31).

There were also significantly more hospitalizations for AMI immediately after the election than before (179 vs. 126 AMI hospitalizations; 204.4 vs. 143.5 per 100,000 PY; RR, 1.42; 95% CI, 1.13-1.79).

There was no significant difference between the risk and control periods for hospitalizations because of stroke or heart failure.

The study also suggests higher rates of acute CVD after the election in older adults, men, and White individuals. Political affiliation was not examined in the study.

“Importantly, results were consistent before and after excluding patients with confirmed COVID-19 infection,” the study team notes.

Yet, the potential influence of COVID-19 stressors on increasing CVD risk cannot be ruled out, they say.

However, COVID-19 stressors occurred over a much longer period and are less likely to explain the transient risks observed in the defined risk and control windows that are in close proximity to the 2020 election, the investigators point out.

There is growing evidence that psychological health contributes to CVD.

Previous studies shown a higher risk for acute CVD around population-wide psychosocial or environmental stressors, but less was known about acute CVD risk in relation to political events.

The researchers note future studies evaluating stress-relieving interventions may be important for understanding the intersection of political events, associated stress, and acute CVD risk.

Partial funding for the study was provided by a grant from the W.K. Kellogg Foundation. The authors have no relevant conflicts of interest.

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