In some cases, bruising or bleeding from bleeding disorders may look like signs of child abuse, but new guidance may help clinicians distinguish one from the other.

On Sept. 19 the American Academy of Pediatrics published two reports – a clinical report and a technical report – in the October 2022 issue of Pediatrics on evaluating for bleeding disorders when child abuse is suspected.

The reports were written by the AAP Section on Hematology/Oncology and the AAP Council on Child Abuse and Neglect.
 

One doesn’t rule out the other

The reports emphasize that laboratory testing of bleeding cannot always rule out abuse, just as a history of trauma (accidental or nonaccidental) may not rule out a bleeding disorder or other medical condition.

In the clinical report, led by James Anderst, MD, MSCI, with the division of child adversity and resilience, Children’s Mercy Hospital, University of Missouri–Kansas City, the researchers note that infants are at especially high risk of abusive bruising/bleeding, but bleeding disorders may also present in infancy.

The authors give an example of a situation when taking a thorough history won’t necessarily rule out a bleeding disorder: Male infants who have been circumcised with no significant bleeding issues may still have a bleeding disorder. Therefore, laboratory evaluations are often needed to detect disordered bleeding.

Children’s medications should be documented, the authors note, because certain drugs, such as nonsteroidal anti-inflammatory drugs, some antibiotics, antiepileptics, and herbal supplements, can affect tests that might be used to detect bleeding disorders.

Likewise, asking about restrictive or unusual diets or alternative therapies is important as some could increase the likelihood of bleeding/bruising.

Signs that bleeding disorder is not likely

The authors advise that, if a child has any of the following, an evaluation for a bleeding disorder is generally not needed:

• Caregivers’ description of trauma sufficiently explains the bruising.
• The child or an independent witness can provide a history of abuse or nonabusive trauma that explains the bruising.
• The outline of the bruising follows an object or hand pattern.
• The location of the bruising is on the ears, neck, or genitals.

“Bruising to the ears, neck, or genitals is rarely seen in either accidental injuries or in children with bleeding disorders,” the authors write.

Specification of which locations for injuries are more indicative of abuse in both mobile and immobile children was among the most important information from the paper, Seattle pediatrician Timothy Joos, MD, said in an interview.

Also very helpful, he said, was the listing of which tests should be done if bruising looks like potential abuse.

The authors write that if bruising is concerning for abuse that necessitates evaluation for bleeding disorders, the following tests should be done: PT (prothrombin time); aPTT (activated partial thromboplastin time); von Willebrand Factor (VWF) activity (Ristocetin cofactor); factor VIII activity level; factor IX activity level; and a complete blood count, including platelets.

“I think that’s what a lot of us suspected, but there’s not a lot of summary evidence regarding that until now,” Dr. Joos said.

Case-by-case decisions on when to test

The decision on whether to evaluate for a bleeding disorder may be made case by case.

If there is no obvious known trauma or intracranial hemorrhage (ICH), particularly subdural hematoma (SDH) in a nonmobile child, abuse should be suspected, the authors write.

They acknowledge that children can have ICH, such as a small SDH or an epidural hematoma, under the point of impact from a short fall.

“However,” the authors write, “short falls rarely result in significant brain injury.”

Conditions may affect screening tests

Screening tests for bleeding disorders can be falsely positive or falsely negative, the authors caution in the technical report, led by Shannon Carpenter, MD, MS, with the department of pediatrics, University of Missouri–Kansas City.

• If coagulation laboratory test specimens sit in a hot metal box all day, for instance, factor levels may be falsely low, the authors explain.
• Conversely, factors such as VWF and factor VIII are acute-phase reactants and factor levels will be deceptively high if blood specimens are taken in a stressful time.
• Patients who have a traumatic brain injury often show temporary coagulopathy that does not signal a congenital disorder.

Vitamin K deficiency

The technical report explains that if an infant, typically younger than 6 months, presents with bleeding/bruising that raises flags for abuse and has a long PT, clinicians should confirm vitamin K was provided at birth and/or testing for vitamin K deficiency should be performed.

Not all states require vitamin K to be administered at birth and some parents refuse it. Deficiency can lead to bleeding in the skin or from mucosal surfaces from circumcision, generalized ecchymoses, and large intramuscular hemorrhages or ICH.

When infants don’t get vitamin K at birth, vitamin K deficiency bleeding (VKDB) is seen most often in the first days of life, the technical report states. It can also occur 1-3 months after birth.

“Late VKDB occurs from the first month to 3 months after birth,” the authors write. “This deficiency is more prevalent in breast-fed babies, because human milk contains less vitamin K than does cow milk.”

Overall, the authors write, extensive lab tests are usually not necessary, given the rarity of most bleeding disorders and specific clinical factors that decrease the odds that a bleeding disorder caused the child’s findings.

Dr. Joos said the decisions described in this paper are the kind that can keep pediatricians up at night.

“Any kind of guidance is helpful in these difficult cases,” he said. “These are scenarios that can often happen in the middle of the night, and you’re often struggling with evidence or past experience that can help you make some of these decisions.”

Authors of the reports and Dr. Joos declared no relevant financial relationships.

In some cases, bruising or bleeding from bleeding disorders may look like signs of child abuse, but new guidance may help clinicians distinguish one from the other.

On Sept. 19 the American Academy of Pediatrics published two reports – a clinical report and a technical report – in the October 2022 issue of Pediatrics on evaluating for bleeding disorders when child abuse is suspected.

The reports were written by the AAP Section on Hematology/Oncology and the AAP Council on Child Abuse and Neglect.
 

One doesn’t rule out the other

The reports emphasize that laboratory testing of bleeding cannot always rule out abuse, just as a history of trauma (accidental or nonaccidental) may not rule out a bleeding disorder or other medical condition.

In the clinical report, led by James Anderst, MD, MSCI, with the division of child adversity and resilience, Children’s Mercy Hospital, University of Missouri–Kansas City, the researchers note that infants are at especially high risk of abusive bruising/bleeding, but bleeding disorders may also present in infancy.

The authors give an example of a situation when taking a thorough history won’t necessarily rule out a bleeding disorder: Male infants who have been circumcised with no significant bleeding issues may still have a bleeding disorder. Therefore, laboratory evaluations are often needed to detect disordered bleeding.

Children’s medications should be documented, the authors note, because certain drugs, such as nonsteroidal anti-inflammatory drugs, some antibiotics, antiepileptics, and herbal supplements, can affect tests that might be used to detect bleeding disorders.

Likewise, asking about restrictive or unusual diets or alternative therapies is important as some could increase the likelihood of bleeding/bruising.

Signs that bleeding disorder is not likely

The authors advise that, if a child has any of the following, an evaluation for a bleeding disorder is generally not needed:

• Caregivers’ description of trauma sufficiently explains the bruising.
• The child or an independent witness can provide a history of abuse or nonabusive trauma that explains the bruising.
• The outline of the bruising follows an object or hand pattern.
• The location of the bruising is on the ears, neck, or genitals.

“Bruising to the ears, neck, or genitals is rarely seen in either accidental injuries or in children with bleeding disorders,” the authors write.

Specification of which locations for injuries are more indicative of abuse in both mobile and immobile children was among the most important information from the paper, Seattle pediatrician Timothy Joos, MD, said in an interview.

Also very helpful, he said, was the listing of which tests should be done if bruising looks like potential abuse.

The authors write that if bruising is concerning for abuse that necessitates evaluation for bleeding disorders, the following tests should be done: PT (prothrombin time); aPTT (activated partial thromboplastin time); von Willebrand Factor (VWF) activity (Ristocetin cofactor); factor VIII activity level; factor IX activity level; and a complete blood count, including platelets.

“I think that’s what a lot of us suspected, but there’s not a lot of summary evidence regarding that until now,” Dr. Joos said.

Case-by-case decisions on when to test

The decision on whether to evaluate for a bleeding disorder may be made case by case.

If there is no obvious known trauma or intracranial hemorrhage (ICH), particularly subdural hematoma (SDH) in a nonmobile child, abuse should be suspected, the authors write.

They acknowledge that children can have ICH, such as a small SDH or an epidural hematoma, under the point of impact from a short fall.

“However,” the authors write, “short falls rarely result in significant brain injury.”

Conditions may affect screening tests

Screening tests for bleeding disorders can be falsely positive or falsely negative, the authors caution in the technical report, led by Shannon Carpenter, MD, MS, with the department of pediatrics, University of Missouri–Kansas City.

• If coagulation laboratory test specimens sit in a hot metal box all day, for instance, factor levels may be falsely low, the authors explain.
• Conversely, factors such as VWF and factor VIII are acute-phase reactants and factor levels will be deceptively high if blood specimens are taken in a stressful time.
• Patients who have a traumatic brain injury often show temporary coagulopathy that does not signal a congenital disorder.

Vitamin K deficiency

The technical report explains that if an infant, typically younger than 6 months, presents with bleeding/bruising that raises flags for abuse and has a long PT, clinicians should confirm vitamin K was provided at birth and/or testing for vitamin K deficiency should be performed.

Not all states require vitamin K to be administered at birth and some parents refuse it. Deficiency can lead to bleeding in the skin or from mucosal surfaces from circumcision, generalized ecchymoses, and large intramuscular hemorrhages or ICH.

When infants don’t get vitamin K at birth, vitamin K deficiency bleeding (VKDB) is seen most often in the first days of life, the technical report states. It can also occur 1-3 months after birth.

“Late VKDB occurs from the first month to 3 months after birth,” the authors write. “This deficiency is more prevalent in breast-fed babies, because human milk contains less vitamin K than does cow milk.”

Overall, the authors write, extensive lab tests are usually not necessary, given the rarity of most bleeding disorders and specific clinical factors that decrease the odds that a bleeding disorder caused the child’s findings.

Dr. Joos said the decisions described in this paper are the kind that can keep pediatricians up at night.

“Any kind of guidance is helpful in these difficult cases,” he said. “These are scenarios that can often happen in the middle of the night, and you’re often struggling with evidence or past experience that can help you make some of these decisions.”

Authors of the reports and Dr. Joos declared no relevant financial relationships.

In some cases, bruising or bleeding from bleeding disorders may look like signs of child abuse, but new guidance may help clinicians distinguish one from the other.

On Sept. 19 the American Academy of Pediatrics published two reports – a clinical report and a technical report – in the October 2022 issue of Pediatrics on evaluating for bleeding disorders when child abuse is suspected.

The reports were written by the AAP Section on Hematology/Oncology and the AAP Council on Child Abuse and Neglect.
 

One doesn’t rule out the other

The reports emphasize that laboratory testing of bleeding cannot always rule out abuse, just as a history of trauma (accidental or nonaccidental) may not rule out a bleeding disorder or other medical condition.

In the clinical report, led by James Anderst, MD, MSCI, with the division of child adversity and resilience, Children’s Mercy Hospital, University of Missouri–Kansas City, the researchers note that infants are at especially high risk of abusive bruising/bleeding, but bleeding disorders may also present in infancy.

The authors give an example of a situation when taking a thorough history won’t necessarily rule out a bleeding disorder: Male infants who have been circumcised with no significant bleeding issues may still have a bleeding disorder. Therefore, laboratory evaluations are often needed to detect disordered bleeding.

Children’s medications should be documented, the authors note, because certain drugs, such as nonsteroidal anti-inflammatory drugs, some antibiotics, antiepileptics, and herbal supplements, can affect tests that might be used to detect bleeding disorders.

Likewise, asking about restrictive or unusual diets or alternative therapies is important as some could increase the likelihood of bleeding/bruising.

Signs that bleeding disorder is not likely

The authors advise that, if a child has any of the following, an evaluation for a bleeding disorder is generally not needed:

• Caregivers’ description of trauma sufficiently explains the bruising.
• The child or an independent witness can provide a history of abuse or nonabusive trauma that explains the bruising.
• The outline of the bruising follows an object or hand pattern.
• The location of the bruising is on the ears, neck, or genitals.

“Bruising to the ears, neck, or genitals is rarely seen in either accidental injuries or in children with bleeding disorders,” the authors write.

Specification of which locations for injuries are more indicative of abuse in both mobile and immobile children was among the most important information from the paper, Seattle pediatrician Timothy Joos, MD, said in an interview.

Also very helpful, he said, was the listing of which tests should be done if bruising looks like potential abuse.

The authors write that if bruising is concerning for abuse that necessitates evaluation for bleeding disorders, the following tests should be done: PT (prothrombin time); aPTT (activated partial thromboplastin time); von Willebrand Factor (VWF) activity (Ristocetin cofactor); factor VIII activity level; factor IX activity level; and a complete blood count, including platelets.

“I think that’s what a lot of us suspected, but there’s not a lot of summary evidence regarding that until now,” Dr. Joos said.

Case-by-case decisions on when to test

The decision on whether to evaluate for a bleeding disorder may be made case by case.

If there is no obvious known trauma or intracranial hemorrhage (ICH), particularly subdural hematoma (SDH) in a nonmobile child, abuse should be suspected, the authors write.

They acknowledge that children can have ICH, such as a small SDH or an epidural hematoma, under the point of impact from a short fall.

“However,” the authors write, “short falls rarely result in significant brain injury.”

Conditions may affect screening tests

Screening tests for bleeding disorders can be falsely positive or falsely negative, the authors caution in the technical report, led by Shannon Carpenter, MD, MS, with the department of pediatrics, University of Missouri–Kansas City.

• If coagulation laboratory test specimens sit in a hot metal box all day, for instance, factor levels may be falsely low, the authors explain.
• Conversely, factors such as VWF and factor VIII are acute-phase reactants and factor levels will be deceptively high if blood specimens are taken in a stressful time.
• Patients who have a traumatic brain injury often show temporary coagulopathy that does not signal a congenital disorder.

Vitamin K deficiency

The technical report explains that if an infant, typically younger than 6 months, presents with bleeding/bruising that raises flags for abuse and has a long PT, clinicians should confirm vitamin K was provided at birth and/or testing for vitamin K deficiency should be performed.

Not all states require vitamin K to be administered at birth and some parents refuse it. Deficiency can lead to bleeding in the skin or from mucosal surfaces from circumcision, generalized ecchymoses, and large intramuscular hemorrhages or ICH.

When infants don’t get vitamin K at birth, vitamin K deficiency bleeding (VKDB) is seen most often in the first days of life, the technical report states. It can also occur 1-3 months after birth.

“Late VKDB occurs from the first month to 3 months after birth,” the authors write. “This deficiency is more prevalent in breast-fed babies, because human milk contains less vitamin K than does cow milk.”

Overall, the authors write, extensive lab tests are usually not necessary, given the rarity of most bleeding disorders and specific clinical factors that decrease the odds that a bleeding disorder caused the child’s findings.

Dr. Joos said the decisions described in this paper are the kind that can keep pediatricians up at night.

“Any kind of guidance is helpful in these difficult cases,” he said. “These are scenarios that can often happen in the middle of the night, and you’re often struggling with evidence or past experience that can help you make some of these decisions.”

Authors of the reports and Dr. Joos declared no relevant financial relationships.

I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”

Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.

Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.

If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
 

Who’s Duke?

Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.

Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.

Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.

“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
 

Your posture may help a pill work better

Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.

The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.

They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)

That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.

In the end, the researchers found that posture can be as significant a factor in how a pill dissolves as gastroparesis, a condition in which the stomach loses the ability to empty properly.
 

How this could help people

Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.

Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.

In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”

As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)

And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.

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

I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”

Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.

Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.

If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
 

Who’s Duke?

Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.

Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.

Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.

“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
 

Your posture may help a pill work better

Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.

The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.

They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)

That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.

In the end, the researchers found that posture can be as significant a factor in how a pill dissolves as gastroparesis, a condition in which the stomach loses the ability to empty properly.
 

How this could help people

Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.

Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.

In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”

As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)

And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.

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

I want to tell you a story about forgetfulness and haste, and how the combination of the two can lead to frightening consequences. A few years ago, I was lying in bed about to turn out the light when I realized I’d forgotten to take “my pill.”

Like some 161 million other American adults, I was then a consumer of a prescription medication. Being conscientious, I got up, retrieved said pill, and tossed it back. Being lazy, I didn’t bother to grab a glass of water to help the thing go down. Instead, I promptly returned to bed, threw a pillow over my head, and prepared for sleep.

Within seconds, I began to feel a burning sensation in my chest. After about a minute, that burn became a crippling pain. Not wanting to alarm my wife, I went into the living room, where I spent the next 30 minutes doubled over in agony. Was I having a heart attack? I phoned my sister, a hospitalist in Texas. She advised me to take myself to the ED to get checked out.

If only I’d known then about “Duke.” He could have told me how critical body posture is when people swallow pills.
 

Who’s Duke?

Duke is a computer representation of a 34-year-old, anatomically normal human male created by computer scientists at the IT’IS Foundation, a nonprofit group based in Switzerland that works on a variety of projects in health care technology. Using Duke, Rajat Mittal, PhD, a professor of medicine at the Johns Hopkins University, Baltimore, created a computer model called “StomachSim” to explore the process of digestion.

Their research, published in the journal Physics of Fluids, turned up several surprising findings about the dynamics of swallowing pills – the most common way medication is used worldwide.

Dr. Mittal said he chose to study the stomach because the functions of most other organ systems, from the heart to the brain, have already attracted plenty of attention from scientists.

“As I was looking to initiate research in some new directions, the implications of stomach biomechanics on important conditions such as diabetes, obesity, and gastroparesis became apparent to me,” he said. “It was clear that bioengineering research in this arena lags other more ‘sexy’ areas such as cardiovascular flows by at least 20 years, and there seemed to be a great opportunity to do impactful work.”
 

Your posture may help a pill work better

Several well-known things affect a pill’s ability to disperse its contents into the gut and be used by the body, such as the stomach’s contents (a heavy breakfast, a mix of liquids like juice, milk, and coffee) and the motion of the organ’s walls. But Dr. Mittal’s group learned that Duke’s posture also played a major role.

The researchers ran Duke through computer simulations in varying postures: upright, leaning right, leaning left, and leaning back, while keeping all the other parts of their analyses (like the things mentioned above) the same.

They found that posture determined as much as 83% of how quickly a pill disperses into the intestines. The most efficient position was leaning right. The least was leaning left, which prevented the pill from reaching the antrum, or bottom section of the stomach, and thus kept all but traces of the dissolved drug from entering the duodenum, where the stomach joins the small intestine. (Interestingly, Jews who observe Passover are advised to recline to the left during the meal as a symbol of freedom and leisure.)

That makes sense if you think about the stomach’s shape, which looks kind of like a bean, curving from the left to the right side of the body. Because of gravity, your position will change where the pill lands.

In the end, the researchers found that posture can be as significant a factor in how a pill dissolves as gastroparesis, a condition in which the stomach loses the ability to empty properly.
 

How this could help people

Among the groups most likely to benefit from such studies, Dr. Mittal said, are the elderly – who both take a lot of pills and are more prone to trouble swallowing because of age-related changes in their esophagus – and the bedridden, who can’t easily shift their posture. The findings may also lead to improvements in the ability to treat people with gastroparesis, a particular problem for people with diabetes.

Future studies with Duke and similar simulations will look at how the GI system digests proteins, carbohydrates, and fatty meals, Dr. Mittal said.

In the meantime, Dr. Mittal offered the following advice: “Standing or sitting upright after taking a pill is fine. If you have to take a pill lying down, stay on your back or on your right side. Avoid lying on your left side after taking a pill.”

As for what happened to me, any gastroenterologist reading this has figured out that my condition was not heart-related. Instead, I likely was having a bout of pill esophagitis, irritation that can result from medications that aggravate the mucosa of the food tube. Although painful, esophagitis isn’t life-threatening. After about an hour, the pain began to subside, and by the next morning I was fine, with only a faint ache in my chest to remind me of my earlier torment. (Researchers noted an increase in the condition early in the COVID-19 pandemic, linked to the antibiotic doxycycline.)

And, in the interest of accuracy, my pill problem began above the stomach. Nothing in the Hopkins research suggests that the alignment of the esophagus plays a role in how drugs disperse in the gut – unless, of course, it prevents those pills from reaching the stomach in the first place.

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

Key clinical point: Astegolimab, despite being well-tolerated, did not lessen the severity of the disease in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the adjusted mean percent changes in the mean Eczema Area and Severity Index score were comparable in the astegolimab (−51.47%) and placebo (−58.24%) groups ( = .5624). A lower proportion of patients who received astegolimab vs placebo reported ≥1 adverse event of grade 1 or 2 severity (41.2% vs 58.1%).

Study details: Findings are from a phase 2 trial including 65 adult patients with moderate-to-severe AD and inadequate response to topical medications who were randomly assigned to receive 490 mg astegolimab or placebo every 4 weeks for 16 weeks and were further followed-up for 8 weeks.

Disclosures: This study was supported by Genentech, Inc. Six authors declared serving as employees of Genentech, Inc., a member of the Roche group, and owning stocks in Roche. The other authors reported ties with several sources, including Roche.

Source: Maurer M et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2022 (Aug 27). Doi: 10.1016/j.jaci.2022.08.015

Key clinical point: Astegolimab, despite being well-tolerated, did not lessen the severity of the disease in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the adjusted mean percent changes in the mean Eczema Area and Severity Index score were comparable in the astegolimab (−51.47%) and placebo (−58.24%) groups ( = .5624). A lower proportion of patients who received astegolimab vs placebo reported ≥1 adverse event of grade 1 or 2 severity (41.2% vs 58.1%).

Study details: Findings are from a phase 2 trial including 65 adult patients with moderate-to-severe AD and inadequate response to topical medications who were randomly assigned to receive 490 mg astegolimab or placebo every 4 weeks for 16 weeks and were further followed-up for 8 weeks.

Disclosures: This study was supported by Genentech, Inc. Six authors declared serving as employees of Genentech, Inc., a member of the Roche group, and owning stocks in Roche. The other authors reported ties with several sources, including Roche.

Source: Maurer M et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2022 (Aug 27). Doi: 10.1016/j.jaci.2022.08.015

Key clinical point: Astegolimab, despite being well-tolerated, did not lessen the severity of the disease in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: At week 16, the adjusted mean percent changes in the mean Eczema Area and Severity Index score were comparable in the astegolimab (−51.47%) and placebo (−58.24%) groups ( = .5624). A lower proportion of patients who received astegolimab vs placebo reported ≥1 adverse event of grade 1 or 2 severity (41.2% vs 58.1%).

Study details: Findings are from a phase 2 trial including 65 adult patients with moderate-to-severe AD and inadequate response to topical medications who were randomly assigned to receive 490 mg astegolimab or placebo every 4 weeks for 16 weeks and were further followed-up for 8 weeks.

Disclosures: This study was supported by Genentech, Inc. Six authors declared serving as employees of Genentech, Inc., a member of the Roche group, and owning stocks in Roche. The other authors reported ties with several sources, including Roche.

Source: Maurer M et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2022 (Aug 27). Doi: 10.1016/j.jaci.2022.08.015

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: A cream containing 1% ectoine and 0.1% hyaluronic acid (EHA) demonstrated superior efficacy than a vehicle cream and was well-tolerated in children aged 2-18 years with mild-to-moderate atopic dermatitis (AD).

Major finding: At week 4, patients receiving EHA cream achieved a significantly higher clinical improvement in SCORing AD (mean difference [MD] −6.62; P < .001) and Investigator’s Global Assessment scores (MD −0.69; P < .001) than those receiving vehicle cream. Mild adverse events like skin erythema, pruritus, and burning skin were reported by 23.5% of patients receiving EHA cream and 5.7% of patients receiving vehicle cream.

Study details: Findings are from an observer-blind, multicenter clinical trial including 57 children aged 2-18 years with mild-to-moderate AD who were randomly assigned to receive EHA or vehicle cream twice daily for 4 weeks.

Disclosures: This study was funded by BODERM SA. The authors declared no conflicts of interest.

Source: Alexopoulos A et al. A randomized, observer-blind, vehicle-control, multi-center clinical investigation for assessing the efficacy and tolerability of a 1% ectoine and hyaluronic acid 0.1%-containing medical device in pediatric patients with mild-to-moderate atopic dermatitis. Pediatr Dermatol. 2022 (Aug 29). Doi: 10.1111/pde.15117

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Ruxolitinib cream demonstrated rapid and sustained improvement in itch in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: A significantly higher proportion of patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream achieved ≥2-point reduction in itch numerical rating scale (NRS2) score as rapidly as within 12 hours (16.3% and 13.1% vs 6.9%; P < .05), with further improvements at week 8 (58.3% and 65.1% vs 29.4%; P < .0001). In patients receiving ruxolitinib (0.75% or 1.5%) vs vehicle cream, time to achieve itch NRS2 score was shorter (5 and 4 vs 17 days).

Study details: Findings are from a pooled analysis of two phase 3 trials, TRuE-AD1 and TRuE-AD2, including 1249 patients with mild-to-moderate AD who were randomly assigned to receive ruxolitinib (0.75% or 1.5%) or vehicle cream twice daily for 8 weeks.

Disclosures: This study was funded by Incyte Corporation. Three authors declared being employees and shareholders of Incyte Corporation. The other authors declared serving as scientific advisors, investigators, or consultants or receiving research grants and honoraria from several sources.

Source: Blauvelt A et al. Rapid pruritus reduction with ruxolitinib cream treatment in patients with atopic dermatitis. J Eur Acad Dermatol Venereol. 2022 (Sep 6). Doi: 10.1111/jdv.18571

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: Topical brepocitinib cream showed significant efficacy in reducing disease severity and was well-tolerated in patients with mild-to-moderate atopic dermatitis (AD).

Major finding: The reduction in the mean Eczema Area and Severity Index at week 6 was significantly higher with 1% brepocitinib cream once daily (QD) vs vehicle QD (−70.1% vs −44.4%) and 1% brepocitinib  cream twice daily (BID) vs vehicle BID (−75.0% vs −47.6%; both P < .05). No serious adverse events or deaths were reported.

Study details: Findings are from a double-blind, dose-ranging, phase 2 study including 292 patients with mild-to-moderate AD who were randomly assigned to receive brepocitinib (0.1% QD, 0.3% QD or BID, 1.0% QD or BID, or 3.0% QD) or vehicle (QD or BID).

Disclosures: This study was sponsored by Pfizer Inc. Nine authors declared being shareholders and current or former employees of Pfizer. The other authors reported ties with several sources, including Pfizer.

Source: Landis MN et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: A phase IIb, randomised, double-blind, vehicle-controlled, dose-ranging, and parallel-group study. Br J Dermatol. 2022 (Aug 20). Doi: 10.1111/bjd.21826

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: The results of this meta-analysis do not demonstrate an elevated risk for incident venous thromboembolism (VTE) in patients with atopic dermatitis (AD), particularly among those receiving treatment with Janus kinase (JAK) inhibitors.

Major finding: The risk for incident VTE was similar among participants with vs without AD (pooled hazard ratio 0.95; 95% CI 0.62-1.45). Among patients with AD who received JAK inhibitors vs placebo /dupilumab, 0.05% vs 0.03% reported VTE (Mantel-Haenszel risk difference 0; 95% CI 0-0).

Study details: Findings are from a meta-analysis of two cohort studies including 458,206 participants with (n = 229,103) and without AD (n = 229,103) and 15 randomized controlled trials including 8787 patients with AD who received an interventional treatment with JAK inhibitors or a control treatment with dupilumab or placebo.

Disclosures: This study did not report any source of funding. The authors declared no conflicts of interest.

Source: Chen TL et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with Janus kinase inhibitors: A systematic review and meta-analysis. JAMA Dermatol. 2022;e223516 (Aug 24). Doi: 10.1001/jamadermatol.2022.3516

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Key clinical point: Dupilumab demonstrated good overall drug survival for up to 3 years in patients with moderate-to-severe atopic dermatitis (AD).

Major finding: Dupilumab showed good overall drug survival rates at 1-year (90.3%), 2-year (85.9%), and 3-year (78.6%). The use of immunosuppressant drugs at baseline was associated with shorter drug survival owing to ineffectiveness (hazard ratio [HR] 2.64; 95% CI 1.10-6.37) and adverse events (HR 2.69; 95% CI 1.32-5.48).

Study details: Findings are from an analysis of the BioDay registry data of 715 adult patients with moderate-to-severe AD who received dupilumab and were followed-up for ≥4 weeks.

Disclosures: The BioDay registry was sponsored by Sanofi Genzyme. The authors declared receiving grants, personal fees, speaking fees, financial support or nonfinancial support from several sources.

Source: Spekhorst LS et al. Dupilumab drug survival and associated predictors in patients with moderate to severe atopic dermatitis: Long-term results from the daily practice BioDay registry. JAMA Dermatol. 2022;e223014 (Aug 10). Doi: 10.1001/jamadermatol.2022.3014

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Add unprovoked venous thromboembolic events to the list of potential consequences of severe obstructive sleep apnea.

That conclusion comes from a study showing that patients with obstructive sleep apnea (OSA) who had the longest nocturnal hypoxemia episodes had a twofold risk for venous thromboembolic events.

The association between nocturnal hypoxemia and VTE was strongest among patients who did not use continuous positive airway pressure (CPAP) systems, reported Wojciech Trzepizur, MD, of Angers University Hospital, France.

Previous studies have suggested links between OSA and both cancer and cognitive decline, but this is the first study to investigate the association between OSA and the incidence of unprovoked VTE, he reported in an oral abstract session at the annual congress of the European Respiratory Society.

“We found that those who spent more than 6% of their nighttime with levels of oxygen in their blood below 90% of normal had an almost twofold risk of developing VTEs compared to patients without oxygen deprivation,” he said.

Dr. Trzepizur and colleagues conducted a retrospective study linking cohort data to an administrative health database. They identified unprovoked VTE in patients with a suspicion for OSA and no previous VTE.

They created Cox proportional hazard models to assess the association of unprovoked VTE with apnea hypopnea index (AHI) measures and nocturnal hypoxemia markers, including the time patients spent below 90% oxygen saturation (T90), oxygen desaturation index (ODI), and hypoxic burden, defined as the total area under the respiratory event-related desaturation curve.

They found that after a median follow-up of 6.3 years, 104 out of 7,355 patients had an unprovoked VTE. In an unadjusted hazard model, there were significant associations between VTE and T90, as well as with hypoxic burden, but not with either AHI or ODI.

However, in an analysis adjusted for age, gender, body mass index, alcohol intake, hypertension, depression, history of cardiovascular disease, statin use, type of sleep study, study site, and CPAP adherence, the investigators found that only T90 remained a significant independent predictor of VTE, with a hazard ratio of 1.06, P = .02.

The association between T90 and VTE strengthened as the time spent below 90% saturation increased. Patients in the highest tercile, who spent more than 6% of the time undersaturated, had an HR for VTE of 1.95 (P = .02), compared with patients with a T90 less than 1%.

There were no significant differences in VTE risk between patients who used CPAP for more than 4 hours per night and those who either used the devices for less than 4 hours or refused CPAP.

“We see that T90 seems to be a strong parameter,” said session comoderator Raphael Heinzer, MD, MPH, of Lausanne University Hospital, Switzerland.

Dr. Heinzer’s comoderator, Silke Ryan, MD, of University College Dublin, pointed out that although T90 was the main predictor of responses, Dr. Trzepizur and colleagues did not control for other pulmonary diseases.

“Obviously, there could be an influence of other hypoxic-related diseases,” she said, and recommended controlling for this in future studies.

Winfried Randerath, MD, of the Bethanien Hospital at the University of Cologne, Germany, head of the ERS specialist group on sleep disordered breathing, said that this study and others presented at the meeting “show worrying associations between obstructive sleep apnea and important diseases that affect survival and quality of life.

“While they cannot prove that OSA causes any of these health problems, people should be made aware of these links and should try to make lifestyle changes in order to reduce their risk of OSA, for instance, by maintaining a healthy weight. However, if OSA is suspected, definite diagnosis and treatment should be initiated. We look forward to further research that may help to clarify whether OSA may be causing some of the health problems seen in these studies,” said Dr. Randerath, who was not involved with the study.

The study was supported by a grant from Institut de Recherche en Santé Respiratoire des Pays de la Loire (IRSR), Beaucouzé, France. Dr. Trzepizur, Dr. Heinzer, Dr. Ryan and Dr. Randerath reported no relevant financial relationships.

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

Adderall, the attention-deficit/hyperactivity disorder medication, is in short supply in some parts of the nation, pharmacy chains and Adderall users say.

Half a dozen people told Bloomberg that pharmacies told them in August and September that the drug was out of stock. The patients were told the drug might not be available for weeks, though it’s supposed to be taken daily. BuzzFeed News said 20 people across the nation said that their pharmacies didn’t have Adderall in stock.

“It’s so frustrating that getting my meds requires me to be organized, focused, and motivated – all the things I’m on these meds to help with,” Irene Kelly, who has been using Adderall for 14 years, told BuzzFeed News.

Two pharmacy chains told Bloomberg that Adderall has not always been available to sell. Walgreens spokesperson Rebekah Pajak said there were “supply chain challenges” affecting instant-release and extended-release versions of the drug. CVS pharmacies can fill Adderall prescriptions “in most cases,” CVS spokesperson Matthew Blanchette said.

Several drugmakers have had brand-name and generic versions of Adderall on back order for months, Bloomberg reported. The problem started with a labor shortage at Teva Pharmaceutical, the top seller of Adderall in the United States, that created a limited supply of brand-name and generic instant-release Adderall, according to the outlet.

That said, the Food and Drug Administration is not reporting an Adderall shortage on its drug shortages database. The federal agency says it lists a drug as being in short supply when “overall market demand is not being met by the manufacturers of the product,” Bloomberg said.

“Manufacturers continue to release product,” FDA spokesperson Cherie Duvall-Jones said, according to Bloomberg.

Demand for Adderall is growing, possibly because of rising ADHD diagnoses that occurred during telehealth medical appointments amid the COVID-19 pandemic, Bloomberg reported, noting that some of those telehealth companies have come under scrutiny by the Drug Enforcement Administration and other government agencies.

NBC News, citing IQVIA, an analytics provider for the life sciences industry, reported that 41.4 million Adderall prescriptions were issued last year, up 10.4% from 2020.

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

Adderall, the attention-deficit/hyperactivity disorder medication, is in short supply in some parts of the nation, pharmacy chains and Adderall users say.

Half a dozen people told Bloomberg that pharmacies told them in August and September that the drug was out of stock. The patients were told the drug might not be available for weeks, though it’s supposed to be taken daily. BuzzFeed News said 20 people across the nation said that their pharmacies didn’t have Adderall in stock.

“It’s so frustrating that getting my meds requires me to be organized, focused, and motivated – all the things I’m on these meds to help with,” Irene Kelly, who has been using Adderall for 14 years, told BuzzFeed News.

Two pharmacy chains told Bloomberg that Adderall has not always been available to sell. Walgreens spokesperson Rebekah Pajak said there were “supply chain challenges” affecting instant-release and extended-release versions of the drug. CVS pharmacies can fill Adderall prescriptions “in most cases,” CVS spokesperson Matthew Blanchette said.

Several drugmakers have had brand-name and generic versions of Adderall on back order for months, Bloomberg reported. The problem started with a labor shortage at Teva Pharmaceutical, the top seller of Adderall in the United States, that created a limited supply of brand-name and generic instant-release Adderall, according to the outlet.

That said, the Food and Drug Administration is not reporting an Adderall shortage on its drug shortages database. The federal agency says it lists a drug as being in short supply when “overall market demand is not being met by the manufacturers of the product,” Bloomberg said.

“Manufacturers continue to release product,” FDA spokesperson Cherie Duvall-Jones said, according to Bloomberg.

Demand for Adderall is growing, possibly because of rising ADHD diagnoses that occurred during telehealth medical appointments amid the COVID-19 pandemic, Bloomberg reported, noting that some of those telehealth companies have come under scrutiny by the Drug Enforcement Administration and other government agencies.

NBC News, citing IQVIA, an analytics provider for the life sciences industry, reported that 41.4 million Adderall prescriptions were issued last year, up 10.4% from 2020.

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

Adderall, the attention-deficit/hyperactivity disorder medication, is in short supply in some parts of the nation, pharmacy chains and Adderall users say.

Half a dozen people told Bloomberg that pharmacies told them in August and September that the drug was out of stock. The patients were told the drug might not be available for weeks, though it’s supposed to be taken daily. BuzzFeed News said 20 people across the nation said that their pharmacies didn’t have Adderall in stock.

“It’s so frustrating that getting my meds requires me to be organized, focused, and motivated – all the things I’m on these meds to help with,” Irene Kelly, who has been using Adderall for 14 years, told BuzzFeed News.

Two pharmacy chains told Bloomberg that Adderall has not always been available to sell. Walgreens spokesperson Rebekah Pajak said there were “supply chain challenges” affecting instant-release and extended-release versions of the drug. CVS pharmacies can fill Adderall prescriptions “in most cases,” CVS spokesperson Matthew Blanchette said.

Several drugmakers have had brand-name and generic versions of Adderall on back order for months, Bloomberg reported. The problem started with a labor shortage at Teva Pharmaceutical, the top seller of Adderall in the United States, that created a limited supply of brand-name and generic instant-release Adderall, according to the outlet.

That said, the Food and Drug Administration is not reporting an Adderall shortage on its drug shortages database. The federal agency says it lists a drug as being in short supply when “overall market demand is not being met by the manufacturers of the product,” Bloomberg said.

“Manufacturers continue to release product,” FDA spokesperson Cherie Duvall-Jones said, according to Bloomberg.

Demand for Adderall is growing, possibly because of rising ADHD diagnoses that occurred during telehealth medical appointments amid the COVID-19 pandemic, Bloomberg reported, noting that some of those telehealth companies have come under scrutiny by the Drug Enforcement Administration and other government agencies.

NBC News, citing IQVIA, an analytics provider for the life sciences industry, reported that 41.4 million Adderall prescriptions were issued last year, up 10.4% from 2020.

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