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Dermatologists skeptical of calamine lotion TikTok trend
Though this may seem to work as a base layer for some people, dermatologists have concerns about this trend, particularly the risk of dryness.
As of Aug. 15, the #calaminelotion tag had more than 20.9 million views on TikTok, with hundreds of videos hailing the cream for its opaque pink tint and matte effect when used under foundation.
Calamine lotion has been used to treat itchy rashes, insect bites, and pain from chickenpox and poison ivy for years. It’s sold over the counter and is a common first-line treatment for skin discomfort that has been used for hundreds of years, says Doris Day, MD, a dermatologist who practices in New York City. It is also on the World Health Organization’s list of essential drugs, she points out in an interview.
“This is something that has been around for a long time. It’s recognized as a drug that has importance. So every now and then, I guess somebody comes across it” and says it’s a “new panacea” for something, “but it’s really not. It’s just an old-time simple product.”
Calamine lotion is made of ferric oxide and zinc oxide, which gives it its antiseptic and anti-itch properties, in addition to its characteristic pink color. Zinc oxide is also commonly used in mineral sunscreens, Dr. Day points out.
Although these ingredients are exceedingly safe with temporary, localized use, high concentrations and chronic use of calamine lotion can be irritating to the skin, says Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington.
At these high concentrations, calamine lotion can be drying, which may cause skin clumping and can be abrasive, says Dr. Sodha. She also cautions that the astringent properties of the zinc and the high pH may disrupt proteins on the skin, which breaks down the skin’s natural defenses. Using calamine lotion all over the face daily can “potentially damage your skin barrier to a point where you’re going to have to do a lot of extra work ... to bring it back,” says Dr. Sodha.
Dr. Day also worries about this trend resulting in dry skin among followers. Even in situations where using calamine lotion is appropriate, like treating poison ivy, its drying effects can sometimes irritate the skin.
And dry skin can be more than an aesthetic issue: It can lead to breaks in the skin, which can result in infections and scarring, she points out. Although this may not occur in someone with extremely oily skin, most people don’t have extremely oily skin, says Dr. Day, so this will be ineffective at best, and at worst, damaging.
If someone is looking for a good makeup base layer, Dr. Sodha recommends something that’s noncomedogenic and nonsensitizing, like silicon-based primers. “The great thing about these products is that they are noncomedogenic, so they won’t clog your pores. They’re synthetic, so they’re not going to cause some sort of allergy,” she says.
In general, both dermatologists warn their patients to be wary of the TikTok trends they see online, and they cautioned about possible effects with long term use of calamine lotion on the face, even if it appears to work with one-time use. “Consumers have to think about this like they do with any sort of product that they come across, just thinking about the long-term effects of something like this and how it works for their own skin,” says Dr. Sodha.
A version of this article first appeared on Medscape.com.
Though this may seem to work as a base layer for some people, dermatologists have concerns about this trend, particularly the risk of dryness.
As of Aug. 15, the #calaminelotion tag had more than 20.9 million views on TikTok, with hundreds of videos hailing the cream for its opaque pink tint and matte effect when used under foundation.
Calamine lotion has been used to treat itchy rashes, insect bites, and pain from chickenpox and poison ivy for years. It’s sold over the counter and is a common first-line treatment for skin discomfort that has been used for hundreds of years, says Doris Day, MD, a dermatologist who practices in New York City. It is also on the World Health Organization’s list of essential drugs, she points out in an interview.
“This is something that has been around for a long time. It’s recognized as a drug that has importance. So every now and then, I guess somebody comes across it” and says it’s a “new panacea” for something, “but it’s really not. It’s just an old-time simple product.”
Calamine lotion is made of ferric oxide and zinc oxide, which gives it its antiseptic and anti-itch properties, in addition to its characteristic pink color. Zinc oxide is also commonly used in mineral sunscreens, Dr. Day points out.
Although these ingredients are exceedingly safe with temporary, localized use, high concentrations and chronic use of calamine lotion can be irritating to the skin, says Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington.
At these high concentrations, calamine lotion can be drying, which may cause skin clumping and can be abrasive, says Dr. Sodha. She also cautions that the astringent properties of the zinc and the high pH may disrupt proteins on the skin, which breaks down the skin’s natural defenses. Using calamine lotion all over the face daily can “potentially damage your skin barrier to a point where you’re going to have to do a lot of extra work ... to bring it back,” says Dr. Sodha.
Dr. Day also worries about this trend resulting in dry skin among followers. Even in situations where using calamine lotion is appropriate, like treating poison ivy, its drying effects can sometimes irritate the skin.
And dry skin can be more than an aesthetic issue: It can lead to breaks in the skin, which can result in infections and scarring, she points out. Although this may not occur in someone with extremely oily skin, most people don’t have extremely oily skin, says Dr. Day, so this will be ineffective at best, and at worst, damaging.
If someone is looking for a good makeup base layer, Dr. Sodha recommends something that’s noncomedogenic and nonsensitizing, like silicon-based primers. “The great thing about these products is that they are noncomedogenic, so they won’t clog your pores. They’re synthetic, so they’re not going to cause some sort of allergy,” she says.
In general, both dermatologists warn their patients to be wary of the TikTok trends they see online, and they cautioned about possible effects with long term use of calamine lotion on the face, even if it appears to work with one-time use. “Consumers have to think about this like they do with any sort of product that they come across, just thinking about the long-term effects of something like this and how it works for their own skin,” says Dr. Sodha.
A version of this article first appeared on Medscape.com.
Though this may seem to work as a base layer for some people, dermatologists have concerns about this trend, particularly the risk of dryness.
As of Aug. 15, the #calaminelotion tag had more than 20.9 million views on TikTok, with hundreds of videos hailing the cream for its opaque pink tint and matte effect when used under foundation.
Calamine lotion has been used to treat itchy rashes, insect bites, and pain from chickenpox and poison ivy for years. It’s sold over the counter and is a common first-line treatment for skin discomfort that has been used for hundreds of years, says Doris Day, MD, a dermatologist who practices in New York City. It is also on the World Health Organization’s list of essential drugs, she points out in an interview.
“This is something that has been around for a long time. It’s recognized as a drug that has importance. So every now and then, I guess somebody comes across it” and says it’s a “new panacea” for something, “but it’s really not. It’s just an old-time simple product.”
Calamine lotion is made of ferric oxide and zinc oxide, which gives it its antiseptic and anti-itch properties, in addition to its characteristic pink color. Zinc oxide is also commonly used in mineral sunscreens, Dr. Day points out.
Although these ingredients are exceedingly safe with temporary, localized use, high concentrations and chronic use of calamine lotion can be irritating to the skin, says Pooja Sodha, MD, director of the Center for Laser and Cosmetic Dermatology at George Washington University, Washington.
At these high concentrations, calamine lotion can be drying, which may cause skin clumping and can be abrasive, says Dr. Sodha. She also cautions that the astringent properties of the zinc and the high pH may disrupt proteins on the skin, which breaks down the skin’s natural defenses. Using calamine lotion all over the face daily can “potentially damage your skin barrier to a point where you’re going to have to do a lot of extra work ... to bring it back,” says Dr. Sodha.
Dr. Day also worries about this trend resulting in dry skin among followers. Even in situations where using calamine lotion is appropriate, like treating poison ivy, its drying effects can sometimes irritate the skin.
And dry skin can be more than an aesthetic issue: It can lead to breaks in the skin, which can result in infections and scarring, she points out. Although this may not occur in someone with extremely oily skin, most people don’t have extremely oily skin, says Dr. Day, so this will be ineffective at best, and at worst, damaging.
If someone is looking for a good makeup base layer, Dr. Sodha recommends something that’s noncomedogenic and nonsensitizing, like silicon-based primers. “The great thing about these products is that they are noncomedogenic, so they won’t clog your pores. They’re synthetic, so they’re not going to cause some sort of allergy,” she says.
In general, both dermatologists warn their patients to be wary of the TikTok trends they see online, and they cautioned about possible effects with long term use of calamine lotion on the face, even if it appears to work with one-time use. “Consumers have to think about this like they do with any sort of product that they come across, just thinking about the long-term effects of something like this and how it works for their own skin,” says Dr. Sodha.
A version of this article first appeared on Medscape.com.
Mindfulness ‘changes the biology’ of pain
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
In a randomized trial, more than 100 healthy individuals were assigned to an 8-week mindfulness-based stress reduction (MBSR) program, a health improvement program (HEP) of the same length, or a waiting list.
Scanning participants’ brains during a heat-based stimulus pain task showed those who completed the MBSR had a reduction in a brain signature linked to the sensory intensity of pain.
“Our finding supports the idea that for new practitioners, mindfulness training directly affects how sensory signals from the body are converted into a brain response,” lead investigator Joseph Wielgosz, PhD, of the Center for Healthy Minds, University of Wisconsin–Madison, said in a release.
Further analysis in long-term meditation practitioners showed the total time spent on intensive retreats was associated with neural changes associated with the perceived stress of pain.
“Just like an experienced athlete plays a sport differently than a first-timer, experienced mindfulness practitioners seem to use their mental ‘muscles’ differently in response to pain than first-time meditators,” Dr. Wielgosz noted.
The findings were published online in the American Journal of Psychiatry.
A complex condition
Dr. Wielgosz told this news organization that pain is “complex,” with multiple stages and several phases between the time signals are sent from pain receptors and the experience of pain.
“The way that mindfulness affects pain processing has more to do with the way the brain interprets pain signals.”
The investigators note that understanding the neurocognitive mechanisms underlying the efficacy of nonpharmacologic pain interventions is a “high-priority objective for improving pain treatment.”
Evidence from brief laboratory interventions and cross-sectional studies suggests that mindfulness training is associated with alterations in both sensory processing and cognitive-emotional regulatory networks, the investigators note.
“However, no such study has yet been conducted on a standardized, full-length, and widely used clinical intervention, such as MBSR,” they add.
Thermal pain task
The randomized, active-control trial included 115 healthy, meditation-naive individuals (61.7% women; average age, 48.3 years). Just over half (58%) had a graduate degree and their mean score on the Hollingshead index was 58.3, indicting a higher socioeconomic status.
All were randomly assigned to an 8-week MBSR course, an 8-week HEP course as an active control group, or a waiting-list control group with no intervention.
The MBSR involved instruction and practice in continuous focused attention on the breath, bodily sensations, and mental content while in seated postures, walking, and doing yoga.
The HEP matched the MBSR in terms of its length, structure, and nonspecific therapeutic elements, which included a supportive group atmosphere, expert instruction, and positive expectancy for benefit.
To examine the interventions’ effect on the pain experience, participants underwent a pain task in which they had 20 thermal stimuli applied to the inside of the left wrist for 12 seconds, including 8 seconds at peak temperature.
The stimuli were separated by a distractor task and intervals for cued anticipation, recovery, and subjective ratings of intensity and unpleasantness on a scale of 0-20.
During the task, participants underwent MRI to assess the neurologic pain signature (NPS) and the stimulus intensity independent pain signature-1 (SIIPS-1) within the brain.
The NPS is activated by various types of pain stimuli, while responding minimally or not at all to “emotionally evocative stimuli” relating to pain or to placebo treatment, the researchers note.
In contrast, the SIIPS-1 is activated in response to aspects of pain unrelated to the stimulus itself. It incorporates a “broader range of cognitive and emotional modulatory circuits,” including those related to expectancy and cognitive processes to modulate the pain experience.
Neural signatures
Results showed that in all groups, age was significantly negatively associated with both NPS (P = .001) and SIIPS-1 response (P < .001), although not subjective pain reports, and was subsequently included in all analyses of neural signatures.
Persons in the MBSR group had a significant decrease in the NPS, compared with those in the HEP group (P = .05), and from pre- to postintervention assessments (P = .023).
Those in the MBSR group also had “marginal” decreases in the NPS vs. the waiting list group (P = .096), and in the SIIPS-1 relative to both the HEP (P = .089) and waiting list groups (P = .087).
In subjective pain ratings, the MBSR group showed a marginal decrease, compared with the waiting list group (P = .078), and from the pre- to postintervention assessments (P = .028).
The HEP group also had marginal decreases in pain unpleasantness vs. the waiting list group (P = .043), and from the pre- to postintervention assessments for pain intensity (P = .046) and unpleasantness (P = .007).
The researchers also assessed 30 long-term meditators who had undertaken at least 3 years of formal experience with meditation, including participating in multiple intensive retreats and ongoing daily practice, and compared them with meditation-naive individuals.
Long-term meditators reported significantly less pain intensity and unpleasantness than those who had not undergone the training (P < .001).
In addition, a higher number of practice hours during a retreat was linked to a greater reduction in pain ratings. This association remained even after adjustment for gender and respiration rate.
However, the number of daily practice hours was not significantly associated with pain ratings among long-term meditators.
Although there were no average differences in neural signature responses between long-term meditators and individuals who were naive to the technique, there was an inverse relationship between hours on retreat and SIIPS-1 response (P = .027).
‘We’re seeing the biology change’
Commenting for this news organization, Fadel Zeidan, PhD, associate professor of anesthesiology, University of California, San Diego, said that in attenuating the experience of pain, mindfulness engages “very novel” mechanisms.
However, the “most remarkable thing about this study” is that the pain effect occurred when the participants were not meditating, “which gives rise to the notion that mental training is just like physical training,” said Dr. Zeidan, who was not involved with the research.
He noted that the notion was not appreciated previously, “because we weren’t able to see the changes,” as they were based on self-report alone.
However, combining those reports with brain imaging and other objective methods means that “we’re actually seeing the biology change,” Dr. Zeidan said.
He added that mindfulness is different from other techniques for modulating the pain experience, because it is self-facilitated.
“People can learn this technique, ideally, for free online. They can learn the recipe, and it’s one of the only techniques out there that can be used immediately to assuage one’s own pain,” he said.
“There’s nothing else out there on this planet that could immediately reduce one’s own pain. You have to wait 45 minutes for Tylenol, distraction can only work for so long, and you can’t really placebo yourself,” Dr. Zeidan added.
The study was funded by a National Center for Complementary and Alternative Medicine grant, National Institute of Mental Health grants, a Fetzer Institute grant, and a John Templeton Foundation grant, as well as a core grant to the Waisman Center from the National Institute of Child Health and Human Development to Albee Messing. Dr. Wielgosz and Dr. Zeidan have reported no relevant financial relationships. Disclosures for the coinvestigators are listed in the original article.
A version of this article first appeared on Medscape.com.
FROM AMERICAN JOURNAL OF PSYCHIATRY
Patients who won’t pay: What’s your recourse?
Owing to the pandemic, job loss, and the possible loss of health insurance, patients have had more difficulty managing copays, coinsurance, and deductibles, not to mention other out-of-pocket health care charges.
“Many of our patients have lost their jobs or have had their hours cut back, and as a result, they are struggling to make ends meet,” said Ahmad Chaudhry, MD, a cardiothoracic surgeon in Lexington, Ky. “However, we cannot continue to provide care if our patients do not pay their bills.”
This news organization asked physicians what they do when their patients don’t pay. About 43% said that they continue to treat them and develop a payment plan; 13% send their bill to collections; 12% continue their care and write off their balance, and 25% choose other actions. Only 8% of physicians drop patients if they don’t pay.
Because you need to pay your own bills, what can you do about nonpaying patients?
Start with price transparency
In the past, patients never knew what their lab work or a chest EKG would cost because it wasn’t listed anywhere, and it was usually more than expected. Because of new legislation concerning health care price transparency, hospitals, health plans, and insurers must pony up with the actual fees, making them transparent to patients. Physician practices should follow suit and keep prices transparent too. Patients are more likely to pay their bills when prepared for the expense.
Patients with insurance often don’t know what they’ll be paying for their visit or their tests because they don’t know how much insurance will cover and what will be left for them to pay. Also, they may not know if they’ve met their deductible yet so they’re unsure whether insurance will even kick in. And patients without insurance still need to know what their costs will be upfront.
According to 10 insights from the Primary Care Consumer Choice Survey, 74% of health care consumers were willing to pay a $50 out-of-pocket charge to know the cost of their primary care visit.
Provide payment plans
Many patients have always needed payment plans. It’s one thing to post a sign at check-in telling patients that all monies are due at the time of service, but it’s another reality for a patient who can’t fork over the $250 charge they just unexpectedly spent in your office.
Discover Financial Services recently ran a survey, with results presented in the press release Americans are Delaying Non-Emergency Medical Care in Higher Numbers than Last Year, and found that many Americans with medical debt are delaying nonemergency medical care. For example, they put off seeing a specialist (52%), seeing a doctor for sickness (41%), and undergoing treatment plans recommended by their doctor (31%).
Turning an account over to collections should be a last resort. In addition, agencies typically charge 30%-40% of the total collected off the top.
Though collecting that amount is better than nothing, using a collection agency may have unexpected consequences. For instance, you’re trusting the agency you hire to collect to represent you and act on your practice’s behalf. If they’re rude or their tactics are harsh in the eyes of the patient or their relatives, it’s your reputation that is on the line.
Rather than use a collection agency, you could collect the payments yourself. When a patient fails to pay within about 3 months, begin mailing statements from the office, followed by firm but generous phone calls trying to collect. Industry estimates put the average cost of sending an invoice, including staff labor, printing, and postage, at about $35 per mailer. Some practices combat the added costs by offering a 20% prompt-pay discount. Offering payment plans is another option that helps garner eventual payment. Plus, practices should direct patients to third-party lenders such as CareCredit for larger bills.
On occasion, some small practices may allow a swap, such as allowing a patient to provide a service such as plumbing, electrical, or painting in exchange for working off the bill. Though it’s not ideal when it comes to finances, you may find it can work in a pinch for a cash-strapped patient. Make sure to keep records of what bills the patient’s work goes toward.
It often helps to incentivize your billing staff to follow up regularly, with various suggestions and tactics, to get patients to pay their bills. The incentive amount you offer will probably be less than if you had to use a collection agency.
Have a payment policy
Because your practice’s primary job is caring for patients’ physical and emotional needs, payment collection without coming off as insensitive can be tricky. “We understand these are difficult times for everyone, and we are doing our best to work with our patients,” said Dr. Chaudhry. Having a written payment policy can help build the bridge. A policy lets patients know what they can expect and can help prevent surprises over what occurs in the event of nonpayment. Your written policy should include:
- When payment is due.
- How the practice handles copays and deductibles.
- What forms of payment are accepted.
- Your policy regarding nonpayment.
Why patients don’t pay
A 2021 Healthcare Consumer Experience Study from Cedar found that medical bills are a source of anxiety and frustration for most patients, affecting their financial experience. More than half of the respondents said that paying a medical bill is stressful. Complicating matters, many health care practices rely on outdated payment systems, which may not provide patients with a clear view of what they owe and how to pay it.
The study found that 53% of respondents find understanding their plan’s coverage and benefits stressful, and 37% of patients won’t pay their bill if they can’t understand it.
People may think the patient is trying to get out of paying, which, of course, is sometimes true, but most of the time they want to pay, concluded the study. Most patients need a better explanation, communication, and accurate accounting of their out-of-pocket costs.
What can doctors do?
If you’re a physician who regularly sees patients who have problems paying their bills, you can take a few steps to minimize the financial impact on your practice:
- Bill the patient’s insurance directly to ensure you receive at least partial payment.
- Keep adequate records of services in case you need to pursue legal action.
- “Be understanding and flexible when it comes to payment arrangements, as this can often be the difference between getting paid and not getting paid at all,” said Dr. Chaudhry.
Distance yourself
When discussing payment policies, physicians should try to distance themselves from the actual collection process as much as possible. Well-meaning physicians often tell patients things like they can “figure something out “ financially or “work them in” during a scheduling conflict, but that often undermines the authority and credibility of the practice’s office staff. Plus, it teaches patients they can get their way if they work on the doctor’s soft spot – something you don’t want to encourage.
By following some of these measures, you can help ensure that your practice continues to thrive despite the challenges posed by nonpaying patients.
A version of this article first appeared on Medscape.com.
Owing to the pandemic, job loss, and the possible loss of health insurance, patients have had more difficulty managing copays, coinsurance, and deductibles, not to mention other out-of-pocket health care charges.
“Many of our patients have lost their jobs or have had their hours cut back, and as a result, they are struggling to make ends meet,” said Ahmad Chaudhry, MD, a cardiothoracic surgeon in Lexington, Ky. “However, we cannot continue to provide care if our patients do not pay their bills.”
This news organization asked physicians what they do when their patients don’t pay. About 43% said that they continue to treat them and develop a payment plan; 13% send their bill to collections; 12% continue their care and write off their balance, and 25% choose other actions. Only 8% of physicians drop patients if they don’t pay.
Because you need to pay your own bills, what can you do about nonpaying patients?
Start with price transparency
In the past, patients never knew what their lab work or a chest EKG would cost because it wasn’t listed anywhere, and it was usually more than expected. Because of new legislation concerning health care price transparency, hospitals, health plans, and insurers must pony up with the actual fees, making them transparent to patients. Physician practices should follow suit and keep prices transparent too. Patients are more likely to pay their bills when prepared for the expense.
Patients with insurance often don’t know what they’ll be paying for their visit or their tests because they don’t know how much insurance will cover and what will be left for them to pay. Also, they may not know if they’ve met their deductible yet so they’re unsure whether insurance will even kick in. And patients without insurance still need to know what their costs will be upfront.
According to 10 insights from the Primary Care Consumer Choice Survey, 74% of health care consumers were willing to pay a $50 out-of-pocket charge to know the cost of their primary care visit.
Provide payment plans
Many patients have always needed payment plans. It’s one thing to post a sign at check-in telling patients that all monies are due at the time of service, but it’s another reality for a patient who can’t fork over the $250 charge they just unexpectedly spent in your office.
Discover Financial Services recently ran a survey, with results presented in the press release Americans are Delaying Non-Emergency Medical Care in Higher Numbers than Last Year, and found that many Americans with medical debt are delaying nonemergency medical care. For example, they put off seeing a specialist (52%), seeing a doctor for sickness (41%), and undergoing treatment plans recommended by their doctor (31%).
Turning an account over to collections should be a last resort. In addition, agencies typically charge 30%-40% of the total collected off the top.
Though collecting that amount is better than nothing, using a collection agency may have unexpected consequences. For instance, you’re trusting the agency you hire to collect to represent you and act on your practice’s behalf. If they’re rude or their tactics are harsh in the eyes of the patient or their relatives, it’s your reputation that is on the line.
Rather than use a collection agency, you could collect the payments yourself. When a patient fails to pay within about 3 months, begin mailing statements from the office, followed by firm but generous phone calls trying to collect. Industry estimates put the average cost of sending an invoice, including staff labor, printing, and postage, at about $35 per mailer. Some practices combat the added costs by offering a 20% prompt-pay discount. Offering payment plans is another option that helps garner eventual payment. Plus, practices should direct patients to third-party lenders such as CareCredit for larger bills.
On occasion, some small practices may allow a swap, such as allowing a patient to provide a service such as plumbing, electrical, or painting in exchange for working off the bill. Though it’s not ideal when it comes to finances, you may find it can work in a pinch for a cash-strapped patient. Make sure to keep records of what bills the patient’s work goes toward.
It often helps to incentivize your billing staff to follow up regularly, with various suggestions and tactics, to get patients to pay their bills. The incentive amount you offer will probably be less than if you had to use a collection agency.
Have a payment policy
Because your practice’s primary job is caring for patients’ physical and emotional needs, payment collection without coming off as insensitive can be tricky. “We understand these are difficult times for everyone, and we are doing our best to work with our patients,” said Dr. Chaudhry. Having a written payment policy can help build the bridge. A policy lets patients know what they can expect and can help prevent surprises over what occurs in the event of nonpayment. Your written policy should include:
- When payment is due.
- How the practice handles copays and deductibles.
- What forms of payment are accepted.
- Your policy regarding nonpayment.
Why patients don’t pay
A 2021 Healthcare Consumer Experience Study from Cedar found that medical bills are a source of anxiety and frustration for most patients, affecting their financial experience. More than half of the respondents said that paying a medical bill is stressful. Complicating matters, many health care practices rely on outdated payment systems, which may not provide patients with a clear view of what they owe and how to pay it.
The study found that 53% of respondents find understanding their plan’s coverage and benefits stressful, and 37% of patients won’t pay their bill if they can’t understand it.
People may think the patient is trying to get out of paying, which, of course, is sometimes true, but most of the time they want to pay, concluded the study. Most patients need a better explanation, communication, and accurate accounting of their out-of-pocket costs.
What can doctors do?
If you’re a physician who regularly sees patients who have problems paying their bills, you can take a few steps to minimize the financial impact on your practice:
- Bill the patient’s insurance directly to ensure you receive at least partial payment.
- Keep adequate records of services in case you need to pursue legal action.
- “Be understanding and flexible when it comes to payment arrangements, as this can often be the difference between getting paid and not getting paid at all,” said Dr. Chaudhry.
Distance yourself
When discussing payment policies, physicians should try to distance themselves from the actual collection process as much as possible. Well-meaning physicians often tell patients things like they can “figure something out “ financially or “work them in” during a scheduling conflict, but that often undermines the authority and credibility of the practice’s office staff. Plus, it teaches patients they can get their way if they work on the doctor’s soft spot – something you don’t want to encourage.
By following some of these measures, you can help ensure that your practice continues to thrive despite the challenges posed by nonpaying patients.
A version of this article first appeared on Medscape.com.
Owing to the pandemic, job loss, and the possible loss of health insurance, patients have had more difficulty managing copays, coinsurance, and deductibles, not to mention other out-of-pocket health care charges.
“Many of our patients have lost their jobs or have had their hours cut back, and as a result, they are struggling to make ends meet,” said Ahmad Chaudhry, MD, a cardiothoracic surgeon in Lexington, Ky. “However, we cannot continue to provide care if our patients do not pay their bills.”
This news organization asked physicians what they do when their patients don’t pay. About 43% said that they continue to treat them and develop a payment plan; 13% send their bill to collections; 12% continue their care and write off their balance, and 25% choose other actions. Only 8% of physicians drop patients if they don’t pay.
Because you need to pay your own bills, what can you do about nonpaying patients?
Start with price transparency
In the past, patients never knew what their lab work or a chest EKG would cost because it wasn’t listed anywhere, and it was usually more than expected. Because of new legislation concerning health care price transparency, hospitals, health plans, and insurers must pony up with the actual fees, making them transparent to patients. Physician practices should follow suit and keep prices transparent too. Patients are more likely to pay their bills when prepared for the expense.
Patients with insurance often don’t know what they’ll be paying for their visit or their tests because they don’t know how much insurance will cover and what will be left for them to pay. Also, they may not know if they’ve met their deductible yet so they’re unsure whether insurance will even kick in. And patients without insurance still need to know what their costs will be upfront.
According to 10 insights from the Primary Care Consumer Choice Survey, 74% of health care consumers were willing to pay a $50 out-of-pocket charge to know the cost of their primary care visit.
Provide payment plans
Many patients have always needed payment plans. It’s one thing to post a sign at check-in telling patients that all monies are due at the time of service, but it’s another reality for a patient who can’t fork over the $250 charge they just unexpectedly spent in your office.
Discover Financial Services recently ran a survey, with results presented in the press release Americans are Delaying Non-Emergency Medical Care in Higher Numbers than Last Year, and found that many Americans with medical debt are delaying nonemergency medical care. For example, they put off seeing a specialist (52%), seeing a doctor for sickness (41%), and undergoing treatment plans recommended by their doctor (31%).
Turning an account over to collections should be a last resort. In addition, agencies typically charge 30%-40% of the total collected off the top.
Though collecting that amount is better than nothing, using a collection agency may have unexpected consequences. For instance, you’re trusting the agency you hire to collect to represent you and act on your practice’s behalf. If they’re rude or their tactics are harsh in the eyes of the patient or their relatives, it’s your reputation that is on the line.
Rather than use a collection agency, you could collect the payments yourself. When a patient fails to pay within about 3 months, begin mailing statements from the office, followed by firm but generous phone calls trying to collect. Industry estimates put the average cost of sending an invoice, including staff labor, printing, and postage, at about $35 per mailer. Some practices combat the added costs by offering a 20% prompt-pay discount. Offering payment plans is another option that helps garner eventual payment. Plus, practices should direct patients to third-party lenders such as CareCredit for larger bills.
On occasion, some small practices may allow a swap, such as allowing a patient to provide a service such as plumbing, electrical, or painting in exchange for working off the bill. Though it’s not ideal when it comes to finances, you may find it can work in a pinch for a cash-strapped patient. Make sure to keep records of what bills the patient’s work goes toward.
It often helps to incentivize your billing staff to follow up regularly, with various suggestions and tactics, to get patients to pay their bills. The incentive amount you offer will probably be less than if you had to use a collection agency.
Have a payment policy
Because your practice’s primary job is caring for patients’ physical and emotional needs, payment collection without coming off as insensitive can be tricky. “We understand these are difficult times for everyone, and we are doing our best to work with our patients,” said Dr. Chaudhry. Having a written payment policy can help build the bridge. A policy lets patients know what they can expect and can help prevent surprises over what occurs in the event of nonpayment. Your written policy should include:
- When payment is due.
- How the practice handles copays and deductibles.
- What forms of payment are accepted.
- Your policy regarding nonpayment.
Why patients don’t pay
A 2021 Healthcare Consumer Experience Study from Cedar found that medical bills are a source of anxiety and frustration for most patients, affecting their financial experience. More than half of the respondents said that paying a medical bill is stressful. Complicating matters, many health care practices rely on outdated payment systems, which may not provide patients with a clear view of what they owe and how to pay it.
The study found that 53% of respondents find understanding their plan’s coverage and benefits stressful, and 37% of patients won’t pay their bill if they can’t understand it.
People may think the patient is trying to get out of paying, which, of course, is sometimes true, but most of the time they want to pay, concluded the study. Most patients need a better explanation, communication, and accurate accounting of their out-of-pocket costs.
What can doctors do?
If you’re a physician who regularly sees patients who have problems paying their bills, you can take a few steps to minimize the financial impact on your practice:
- Bill the patient’s insurance directly to ensure you receive at least partial payment.
- Keep adequate records of services in case you need to pursue legal action.
- “Be understanding and flexible when it comes to payment arrangements, as this can often be the difference between getting paid and not getting paid at all,” said Dr. Chaudhry.
Distance yourself
When discussing payment policies, physicians should try to distance themselves from the actual collection process as much as possible. Well-meaning physicians often tell patients things like they can “figure something out “ financially or “work them in” during a scheduling conflict, but that often undermines the authority and credibility of the practice’s office staff. Plus, it teaches patients they can get their way if they work on the doctor’s soft spot – something you don’t want to encourage.
By following some of these measures, you can help ensure that your practice continues to thrive despite the challenges posed by nonpaying patients.
A version of this article first appeared on Medscape.com.
A 9-year-old girl was evaluated for a week-long history of rash on the feet
A complete body examination failed to reveal any other lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. She was diagnosed with cutaneous larva migrans (CLM) given the clinical appearance of the lesions and the recent travel history.
CLM is a zoonotic infection caused by several hookworms such as Ancylostoma braziliense, Ancylostoma caninum, and Uncinaria stenocephala, as well as human hookworms such as Ancylostoma duodenale and Necator americanus. The hookworms can be present in contaminated soils and sandy beaches on the coastal regions of South America, the Caribbean, the Southeastern United States, Southeast Asia, and Africa.1-5
It is a common disease in the tourist population visiting tropical countries because of exposure to the hookworms in the soil without use of proper foot protection.
The clinical features are of an erythematous linear serpiginous plaque that is pruritic and can progress from millimeters to centimeters in size within a few days to weeks. Vesicles and multiple tracks can also be seen. The most common locations are the feet, buttocks, and thighs.
The larvae in the soil come from eggs excreted in the feces of infected cats and dogs. The infection is caused by direct contact of the larvae with the stratum corneum of the skin creating a burrow and an inflammatory response that will cause erythema, edema, track formation, and pruritus.
Diagnosis is made clinically. Rarely, a skin biopsy is warranted. The differential diagnosis includes tinea pedis, granuloma annulare, larva currens, contact dermatitis, and herpes zoster.
Tinea pedis is a fungal infection of the skin of the feet, commonly localized on the web spaces. The risk factors are a hot and humid environment, prolonged wear of occlusive footwear, excess sweating, and prolonged exposure to water.6 Diagnosis is confirmed by microscopic evaluation of skin scrapings with potassium hydroxide or a fungal culture. The infection is treated with topical antifungal creams and, in severe cases, systemic antifungals. Granuloma annulare is a benign chronic skin condition that presents with annular-shaped lesions. Its etiology is unknown. The lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The feature distinguishing granuloma annulare from other annular lesions is its absence of scale.
Allergic contact dermatitis is caused by skin exposure to an allergen and a secondary inflammatory response to this material on the skin causing inflammation, vesiculation, and pruritus. Lesions are treated with topical corticosteroids and avoidance of the allergen.
Herpes zoster is caused by a viral infection of the latent varicella-zoster virus. Its reactivation causes the presence of vesicles with an erythematous base that have a dermatomal distribution. The lesions are usually tender. Treatment is recommended to be started within 72 hours of the eruption with antivirals such as acyclovir or valacyclovir.
Cutaneous larva currens is caused by the cutaneous infection with Strongyloides stercoralis. In comparison with CLM, the lesions progress faster, at up to a centimeter within hours.
CLM is usually self-limited. If the patient has multiple lesions or more severe disease, oral albendazole or ivermectin can be prescribed. Other treatments, though not preferred, include freezing and topical thiabendazole solutions.
As our patient had several lesions, oral ivermectin was chosen as treatment and the lesions cleared within a week. Also, she was recommended to always wear shoes when walking on the beach.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Dr. Valderrama is a pediatric dermatologist at Fundación Cardioinfantil, Bogota, Colombia.
References
1. Feldmeier H and Schuster A. Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):915-8.
2. Jacobson CC and Abel EA. J Am Acad Dermatol. 2007 Jun;56(6):1026-43.
3. Kincaid L et al. Travel Med Infect Dis. 2015 Sep-Oct;13(5):382-7.
4. Gill N et al. Adv Skin Wound Care. 2020 Jul;33(7):356-9.
5. Rodenas-Herranz T et al. Dermatol Ther. 2020 May;33(3):e13316.
6. Pramod K et al. In: StatPearls [Internet]. Treasure Island (Fla): StatPearls Publishing; 2022 Jan.
A complete body examination failed to reveal any other lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. She was diagnosed with cutaneous larva migrans (CLM) given the clinical appearance of the lesions and the recent travel history.
CLM is a zoonotic infection caused by several hookworms such as Ancylostoma braziliense, Ancylostoma caninum, and Uncinaria stenocephala, as well as human hookworms such as Ancylostoma duodenale and Necator americanus. The hookworms can be present in contaminated soils and sandy beaches on the coastal regions of South America, the Caribbean, the Southeastern United States, Southeast Asia, and Africa.1-5
It is a common disease in the tourist population visiting tropical countries because of exposure to the hookworms in the soil without use of proper foot protection.
The clinical features are of an erythematous linear serpiginous plaque that is pruritic and can progress from millimeters to centimeters in size within a few days to weeks. Vesicles and multiple tracks can also be seen. The most common locations are the feet, buttocks, and thighs.
The larvae in the soil come from eggs excreted in the feces of infected cats and dogs. The infection is caused by direct contact of the larvae with the stratum corneum of the skin creating a burrow and an inflammatory response that will cause erythema, edema, track formation, and pruritus.
Diagnosis is made clinically. Rarely, a skin biopsy is warranted. The differential diagnosis includes tinea pedis, granuloma annulare, larva currens, contact dermatitis, and herpes zoster.
Tinea pedis is a fungal infection of the skin of the feet, commonly localized on the web spaces. The risk factors are a hot and humid environment, prolonged wear of occlusive footwear, excess sweating, and prolonged exposure to water.6 Diagnosis is confirmed by microscopic evaluation of skin scrapings with potassium hydroxide or a fungal culture. The infection is treated with topical antifungal creams and, in severe cases, systemic antifungals. Granuloma annulare is a benign chronic skin condition that presents with annular-shaped lesions. Its etiology is unknown. The lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The feature distinguishing granuloma annulare from other annular lesions is its absence of scale.
Allergic contact dermatitis is caused by skin exposure to an allergen and a secondary inflammatory response to this material on the skin causing inflammation, vesiculation, and pruritus. Lesions are treated with topical corticosteroids and avoidance of the allergen.
Herpes zoster is caused by a viral infection of the latent varicella-zoster virus. Its reactivation causes the presence of vesicles with an erythematous base that have a dermatomal distribution. The lesions are usually tender. Treatment is recommended to be started within 72 hours of the eruption with antivirals such as acyclovir or valacyclovir.
Cutaneous larva currens is caused by the cutaneous infection with Strongyloides stercoralis. In comparison with CLM, the lesions progress faster, at up to a centimeter within hours.
CLM is usually self-limited. If the patient has multiple lesions or more severe disease, oral albendazole or ivermectin can be prescribed. Other treatments, though not preferred, include freezing and topical thiabendazole solutions.
As our patient had several lesions, oral ivermectin was chosen as treatment and the lesions cleared within a week. Also, she was recommended to always wear shoes when walking on the beach.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Dr. Valderrama is a pediatric dermatologist at Fundación Cardioinfantil, Bogota, Colombia.
References
1. Feldmeier H and Schuster A. Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):915-8.
2. Jacobson CC and Abel EA. J Am Acad Dermatol. 2007 Jun;56(6):1026-43.
3. Kincaid L et al. Travel Med Infect Dis. 2015 Sep-Oct;13(5):382-7.
4. Gill N et al. Adv Skin Wound Care. 2020 Jul;33(7):356-9.
5. Rodenas-Herranz T et al. Dermatol Ther. 2020 May;33(3):e13316.
6. Pramod K et al. In: StatPearls [Internet]. Treasure Island (Fla): StatPearls Publishing; 2022 Jan.
A complete body examination failed to reveal any other lesions suggestive of a fungal infection. A blood count and urinalysis were within normal limits. She had no lymphadenopathy or hepatosplenomegaly. She was diagnosed with cutaneous larva migrans (CLM) given the clinical appearance of the lesions and the recent travel history.
CLM is a zoonotic infection caused by several hookworms such as Ancylostoma braziliense, Ancylostoma caninum, and Uncinaria stenocephala, as well as human hookworms such as Ancylostoma duodenale and Necator americanus. The hookworms can be present in contaminated soils and sandy beaches on the coastal regions of South America, the Caribbean, the Southeastern United States, Southeast Asia, and Africa.1-5
It is a common disease in the tourist population visiting tropical countries because of exposure to the hookworms in the soil without use of proper foot protection.
The clinical features are of an erythematous linear serpiginous plaque that is pruritic and can progress from millimeters to centimeters in size within a few days to weeks. Vesicles and multiple tracks can also be seen. The most common locations are the feet, buttocks, and thighs.
The larvae in the soil come from eggs excreted in the feces of infected cats and dogs. The infection is caused by direct contact of the larvae with the stratum corneum of the skin creating a burrow and an inflammatory response that will cause erythema, edema, track formation, and pruritus.
Diagnosis is made clinically. Rarely, a skin biopsy is warranted. The differential diagnosis includes tinea pedis, granuloma annulare, larva currens, contact dermatitis, and herpes zoster.
Tinea pedis is a fungal infection of the skin of the feet, commonly localized on the web spaces. The risk factors are a hot and humid environment, prolonged wear of occlusive footwear, excess sweating, and prolonged exposure to water.6 Diagnosis is confirmed by microscopic evaluation of skin scrapings with potassium hydroxide or a fungal culture. The infection is treated with topical antifungal creams and, in severe cases, systemic antifungals. Granuloma annulare is a benign chronic skin condition that presents with annular-shaped lesions. Its etiology is unknown. The lesions may be asymptomatic or mildly pruritic. Localized granuloma annulare typically presents as reddish-brown papules or plaques on the fingers, hands, elbows, dorsal feet, or ankles. The feature distinguishing granuloma annulare from other annular lesions is its absence of scale.
Allergic contact dermatitis is caused by skin exposure to an allergen and a secondary inflammatory response to this material on the skin causing inflammation, vesiculation, and pruritus. Lesions are treated with topical corticosteroids and avoidance of the allergen.
Herpes zoster is caused by a viral infection of the latent varicella-zoster virus. Its reactivation causes the presence of vesicles with an erythematous base that have a dermatomal distribution. The lesions are usually tender. Treatment is recommended to be started within 72 hours of the eruption with antivirals such as acyclovir or valacyclovir.
Cutaneous larva currens is caused by the cutaneous infection with Strongyloides stercoralis. In comparison with CLM, the lesions progress faster, at up to a centimeter within hours.
CLM is usually self-limited. If the patient has multiple lesions or more severe disease, oral albendazole or ivermectin can be prescribed. Other treatments, though not preferred, include freezing and topical thiabendazole solutions.
As our patient had several lesions, oral ivermectin was chosen as treatment and the lesions cleared within a week. Also, she was recommended to always wear shoes when walking on the beach.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. Dr. Valderrama is a pediatric dermatologist at Fundación Cardioinfantil, Bogota, Colombia.
References
1. Feldmeier H and Schuster A. Eur J Clin Microbiol Infect Dis. 2012 Jun;31(6):915-8.
2. Jacobson CC and Abel EA. J Am Acad Dermatol. 2007 Jun;56(6):1026-43.
3. Kincaid L et al. Travel Med Infect Dis. 2015 Sep-Oct;13(5):382-7.
4. Gill N et al. Adv Skin Wound Care. 2020 Jul;33(7):356-9.
5. Rodenas-Herranz T et al. Dermatol Ther. 2020 May;33(3):e13316.
6. Pramod K et al. In: StatPearls [Internet]. Treasure Island (Fla): StatPearls Publishing; 2022 Jan.
Her mother reported recent travel to a beachside city in Colombia. A review of systems was negative. She was not taking any other medications or vitamin supplements. There were no pets at home and no other affected family members. Physical exam was notable for an erythematous curvilinear plaque on the feet and a small vesicle.
Ultrasound on par with CT for evaluating sarcopenia in patients with cirrhosis
Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.
US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.
“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”
To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm2/m2 for women and 50 cm2/m2 for men.
US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).
Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).
The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.
“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”
According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”
In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.
“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.
Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.
US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.
“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”
To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm2/m2 for women and 50 cm2/m2 for men.
US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).
Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).
The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.
“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”
According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”
In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.
“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.
Using ultrasound (US) to evaluate sarcopenic obesity in patients with cirrhosis may offer accuracy on par with computed tomography (CT), according to investigators.
US-based assessment presents a more affordable point-of-care strategy that limits radiation exposure, which enables sequential monitoring, reported lead author Sukhpal Dhariwal, MBBS, MD, of the Postgraduate Institute of Medical Education and Research, Chandigarh, India.
“Preliminary data in patients with liver disease ... suggest that US muscle assessment–derived indices, especially thigh muscle thickness, identify sarcopenia CT-skeletal muscle index (SMI) and also predict hospitalization and mortality,” the investigators wrote in Journal of Clinical Gastroenterology. “However, the applicability of US-based techniques to measure muscle mass in the high-risk group of patients with cirrhosis and sarcopenic obesity has not been evaluated.”
To address this knowledge gap, the investigators performed both US- and CT-based muscle assessments in 52 patients with obesity and evidence of cirrhosis; 40 patients were male and the mean age was 50.9 years. In all, 20 (38.5%) were diagnosed with sarcopenia based on CT-determined SMI scores of less than 39 cm2/m2 for women and 50 cm2/m2 for men.
US showed that it was similarly capable of categorizing patients. The modality significantly differentiated individuals with or without sarcopenia based on high area under the curve values in four muscle indices: quadriceps muscle thickness (0.98), quadriceps muscle feather index (0.95), forearm muscle thickness (0.85), and forearm feather index (0.80).
Direct comparison of US-based assessment against CT-based SMI revealed positive correlations, with significant r values ranging from 0.40 to 0.58. These correlations were stronger in a male-only subgroup analysis, in which r values ranged from 0.52 to 0.70. R values were not calculated in the female subgroup because of the small sample size (n = 12).
The investigators adjusted indices for height, which may pose bias for overestimating muscle mass. Another limitation is the small sample size.
“US-based assessment of sarcopenia has excellent diagnostic accuracy and correlates highly with cross-sectional imaging-based SMI in cirrhosis patients with sarcopenic obesity,” the investigators concluded. “US may serve as an easy-to-use, point-of-care tool for assessing sarcopenia in sarcopenic obesity with the advantage of repeated sequential assessment.”
According to Jamile Wakim-Fleming, MD, of the Cleveland Clinic, “US-based muscle mass assessment seems to be reliable, reproducible, and simple to perform and should be encouraged along with nutrition assessments in all patients with cirrhosis and obesity.”
In a written comment, Dr. Wakim-Fleming noted the importance of timely monitoring and intervention in this patient population.
“Considering the morbidity and the poor outcomes associated with sarcopenic obesity and its frequency in cirrhosis, it is important to make early diagnosis and institute a management plan to improve muscle mass and function,” she said.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Wakim-Fleming reported no relevant conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Phase 3 data: Zanubrutinib bests standard CLL treatment
At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.
Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.
According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”
However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.
In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”
The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.
The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.
The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.
At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).
In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.
The researchers wrote that “zanubrutinib showed superior progression-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)–positive disease.”
The study didn’t examine cost; zanubrutinib is quite expensive.
In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.
“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”
In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”
“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”
The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.
At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.
Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.
According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”
However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.
In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”
The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.
The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.
The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.
At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).
In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.
The researchers wrote that “zanubrutinib showed superior progression-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)–positive disease.”
The study didn’t examine cost; zanubrutinib is quite expensive.
In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.
“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”
In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”
“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”
The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.
At a median follow-up of 26.2 months, progression to worsening disease or death was much lower in patients with these conditions who took zanubrutinib (Brukinsa), compared with those who took bendamustine-rituximab (hazard ratio. 0.42; 95% confidence interval, 0.28-0.63; P < .00011). The study was published in The Lancet Oncology.
Researchers already knew that ibrutinib, another BTKi, improves progression-free survival, study coauthor Paolo Ghia, MD, PhD, professor of medical oncology at Vita-Salute San Raffaele University, Milan, said in an interview. “Now we confirmed that the same advantage can be seen” in zanubrutinib.
According to Dr. Ghia, bendamustine-rituximab has long been a standard treatment in blood cancers and is considered well tolerated and inexpensive. But BTKis such as first-in-line ibrutinib have shown better results, he said, “and progressively, we are going to abandon bendamustine-rituximab.”
However, ibrutinib causes significant adverse effects such as bleeding, worsening hypertension and arrhythmia, he noted. As a result, second-generation BTKi such as zanubrutinib have entered the picture. The Food and Drug Administration approved it in 2019 for mantle cell lymphoma, and it has since been approved for Waldenström’s macroglobulinemia and marginal zone lymphoma.
In 2021, an interim analysis in a trial of the drug in patients with previously treated CLL, compared with ibrutinib, found that “zanubrutinib was shown to have a superior response rate, an improved PFS, and a lower rate of atrial fibrillation/flutter.”
The drug’s manufacturer, BeiGene, launched the new open-label, multicenter study, in a bid for FDA approval of the drug as a frontline treatment for CLL and SLL. More than 150 hospitals in 14 countries participated in the trial from 2017 to 2019.
The subjects were all adults and at least 65 years old or with comorbidities; None had the genetic trait del(17)(p13.1); 241 were assigned to take zanubrutinib and 238 to bendamustine-rituximab. Another group consisted of 111 patients with CLL and del(17)(p13·1). According to the study authors, these patients are especially difficult to treat.
The vast majority of patients were White (92%-95% depending on group) and male (61%-71%); 90%-92% had CLL.
At follow-up, there was no difference in overall survival between the main zanubrutinib and bendamustine-rituximab groups; 29 (12%) of the 241 patients in the zanubrutinib group and 57 (24%) of 238 patients in the bendamustine-rituximab group had progressed or died (HR, 0.42; 95% CI, 0.27-0.66; P < .00011). Adverse events leading to discontinuation were more common in the bendamustine-rituximab group (14%) versus zanubrutinib (8%).
In the third group, which only received zanubrutinib, 14% of patients died at median follow-up of 30.5 months; 98% of patients had adverse effects, and 5% discontinued treatment.
The researchers wrote that “zanubrutinib showed superior progression-free survival versus bendamustine-rituximab in older patients or those with comorbidities with untreated CLL, with a low incidence of cardiac arrhythmia. Similar efficacy was observed in patients with del(17p)–positive disease.”
The study didn’t examine cost; zanubrutinib is quite expensive.
In an interview, hematologist-oncologist Anthony Mato, MD, of Memorial Sloan Kettering Cancer Center in New York said the new study is important although not surprising, since other medications in the same class have shown similar results. Zanubrutinib is an alternative to ibrutinib, although the latter remains “an excellent drug,” he said.
“The era of chemotherapy being a first choice is over,” he said. “We’ve had several randomized studies that show targeted therapies are better tolerated and have better outcomes. We now need to look through the choices to decide which one of these good options are the best for our patients.”
In an interview, hematologist-oncologist Joanna Rhodes, MD, of Northwell Health in Hempstead, N.Y., highlighted the side effect profile of zanubrutinib, noting that it is low and resembles that of other BTKis, making it “another excellent treatment option.”
“We are seeing that bruising, upper respiratory tract infections, diarrhea, and arthralgias are the most common side effects,” she said. “Bleeding also is a common side effect, which is consistent across the class of BTKis, with 5% of patients developing a major bleed. Also, 3% of patients treated with zanubrutinib developed atrial fibrillation, which is consistent with data from other trials. Treatment discontinuation rates were low (8%).”
The study was funded by BeiGene. The authors reported multiple disclosures. Dr. Mato reported research or consulting relationships with BeiGene, AstraZeneca, and AbbVie. Dr. Rhodes reported multiple research or consulting relationships with Abbvie, BeiGene, Genentech, and others.
FROM THE LANCET ONCOLOGY
Guidelines: Convalescent plasma not recommended for most hospitalized with COVID
In summarizing the practice statement, the authors write, “CCP is most effective when transfused with high neutralizing titers early after symptom onset.”
The five guidelines, were published in Annals of Internal Medicine. The guidelines and strength of recommendations are:
- Nonhospitalized patients at high risk for disease progression should have CCP transfusion in addition to usual standard of care. (weak)
- CCP transfusion should not be done for unselected hospitalized patients with moderate or severe disease. This does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. (strong)
- CCP transfusion is suggested in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies at admission. (weak)
- Prophylactic CCP transfusion is not recommended for uninfected people with close contact exposure to someone with COVID-19. (weak)
- The AABB suggests CCP transfusion along with standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression. (weak)
Multiple guidelines for use of CCP are similar
In an accompanying editorial, Jason V. Baker, MD, MS, and H. Clifford Lane, MD, who are part of the National Institutes of Health Treatment Guidelines Panel, say guidelines from that organization around CCP generally align with those of the AABB and the Infectious Diseases Society of America.
They all note CCP’s potential for helping immunocompromised patients and they recommend against CCP in unselected, hospitalized patients.
The main difference is that the AABB also “suggests” using CCP in combination with other standard treatments for outpatients at high risk for disease progression, regardless of their immune status, write Dr. Baker, who is with Hennepin Healthcare and the department of medicine at the University of Minnesota in Minneapolis, and Dr. Lane, who is with the National Institutes of Health.
The precise circumstance for recommending CCP remains unclear, Dr. Baker and Dr. Lane write. That’s because most available evidence has come in the absence of vaccines and antiviral agents, including nirmatrelvir–ritonavir (Paxlovid), they explain.
“At this point in the pandemic, it seems that the patient most likely to benefit from passive antibody therapy is the immunocompromised host with COVID-19 who cannot mount their own antibody response to vaccine or prior infection,” they write.
“In that setting, and in the absence of other antiviral treatments or progression despite receipt of standard treatments, high-titer CCP from a recently recovered donor is a reasonable approach,” they conclude.
Eileen Barrett, MD, MPH, an assistant professor in the division of hospital medicine at the University of New Mexico in Albuquerque, said in an interview that “clinical guidelines like this really help practicing physicians as we navigate the explosion of research findings since the start of the pandemic.”
One strong recommendation
Dr. Barrett pointed out that four of the five recommendations are rated “weak.”
“The weak recommendations for convalescent plasma in most situations is very humbling,” she said, “particularly as we recall the earliest days of the pandemic when many hospitalized patients received this treatment when little was known about what could help.”
She highlighted the paper’s only strong recommendation, which was against convalescent plasma use for the vast majority of hospitalized patients with COVID.
“That clinical bottom line is what most clinicians will look for,” she said.
“Similarly,” she said, “the accompanying editorial is so helpful in reminding the reader that, despite some possible benefit to convalescent plasma in a smaller subgroup of patients, variant-appropriate monoclonal antibodies and antivirals are better options.”
The disclosures for lead author of the guidelines, Lise J. Estcourt, MB BChir, DPhil, with the National Health Service Blood and Transplant Department and Radcliffe department of medicine at the University of Oxford (England) and her colleagues are available at https://rmed.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1079. The editorialists and Dr. Barrett declare no relevant financial relationships.
In summarizing the practice statement, the authors write, “CCP is most effective when transfused with high neutralizing titers early after symptom onset.”
The five guidelines, were published in Annals of Internal Medicine. The guidelines and strength of recommendations are:
- Nonhospitalized patients at high risk for disease progression should have CCP transfusion in addition to usual standard of care. (weak)
- CCP transfusion should not be done for unselected hospitalized patients with moderate or severe disease. This does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. (strong)
- CCP transfusion is suggested in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies at admission. (weak)
- Prophylactic CCP transfusion is not recommended for uninfected people with close contact exposure to someone with COVID-19. (weak)
- The AABB suggests CCP transfusion along with standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression. (weak)
Multiple guidelines for use of CCP are similar
In an accompanying editorial, Jason V. Baker, MD, MS, and H. Clifford Lane, MD, who are part of the National Institutes of Health Treatment Guidelines Panel, say guidelines from that organization around CCP generally align with those of the AABB and the Infectious Diseases Society of America.
They all note CCP’s potential for helping immunocompromised patients and they recommend against CCP in unselected, hospitalized patients.
The main difference is that the AABB also “suggests” using CCP in combination with other standard treatments for outpatients at high risk for disease progression, regardless of their immune status, write Dr. Baker, who is with Hennepin Healthcare and the department of medicine at the University of Minnesota in Minneapolis, and Dr. Lane, who is with the National Institutes of Health.
The precise circumstance for recommending CCP remains unclear, Dr. Baker and Dr. Lane write. That’s because most available evidence has come in the absence of vaccines and antiviral agents, including nirmatrelvir–ritonavir (Paxlovid), they explain.
“At this point in the pandemic, it seems that the patient most likely to benefit from passive antibody therapy is the immunocompromised host with COVID-19 who cannot mount their own antibody response to vaccine or prior infection,” they write.
“In that setting, and in the absence of other antiviral treatments or progression despite receipt of standard treatments, high-titer CCP from a recently recovered donor is a reasonable approach,” they conclude.
Eileen Barrett, MD, MPH, an assistant professor in the division of hospital medicine at the University of New Mexico in Albuquerque, said in an interview that “clinical guidelines like this really help practicing physicians as we navigate the explosion of research findings since the start of the pandemic.”
One strong recommendation
Dr. Barrett pointed out that four of the five recommendations are rated “weak.”
“The weak recommendations for convalescent plasma in most situations is very humbling,” she said, “particularly as we recall the earliest days of the pandemic when many hospitalized patients received this treatment when little was known about what could help.”
She highlighted the paper’s only strong recommendation, which was against convalescent plasma use for the vast majority of hospitalized patients with COVID.
“That clinical bottom line is what most clinicians will look for,” she said.
“Similarly,” she said, “the accompanying editorial is so helpful in reminding the reader that, despite some possible benefit to convalescent plasma in a smaller subgroup of patients, variant-appropriate monoclonal antibodies and antivirals are better options.”
The disclosures for lead author of the guidelines, Lise J. Estcourt, MB BChir, DPhil, with the National Health Service Blood and Transplant Department and Radcliffe department of medicine at the University of Oxford (England) and her colleagues are available at https://rmed.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1079. The editorialists and Dr. Barrett declare no relevant financial relationships.
In summarizing the practice statement, the authors write, “CCP is most effective when transfused with high neutralizing titers early after symptom onset.”
The five guidelines, were published in Annals of Internal Medicine. The guidelines and strength of recommendations are:
- Nonhospitalized patients at high risk for disease progression should have CCP transfusion in addition to usual standard of care. (weak)
- CCP transfusion should not be done for unselected hospitalized patients with moderate or severe disease. This does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. (strong)
- CCP transfusion is suggested in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies at admission. (weak)
- Prophylactic CCP transfusion is not recommended for uninfected people with close contact exposure to someone with COVID-19. (weak)
- The AABB suggests CCP transfusion along with standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression. (weak)
Multiple guidelines for use of CCP are similar
In an accompanying editorial, Jason V. Baker, MD, MS, and H. Clifford Lane, MD, who are part of the National Institutes of Health Treatment Guidelines Panel, say guidelines from that organization around CCP generally align with those of the AABB and the Infectious Diseases Society of America.
They all note CCP’s potential for helping immunocompromised patients and they recommend against CCP in unselected, hospitalized patients.
The main difference is that the AABB also “suggests” using CCP in combination with other standard treatments for outpatients at high risk for disease progression, regardless of their immune status, write Dr. Baker, who is with Hennepin Healthcare and the department of medicine at the University of Minnesota in Minneapolis, and Dr. Lane, who is with the National Institutes of Health.
The precise circumstance for recommending CCP remains unclear, Dr. Baker and Dr. Lane write. That’s because most available evidence has come in the absence of vaccines and antiviral agents, including nirmatrelvir–ritonavir (Paxlovid), they explain.
“At this point in the pandemic, it seems that the patient most likely to benefit from passive antibody therapy is the immunocompromised host with COVID-19 who cannot mount their own antibody response to vaccine or prior infection,” they write.
“In that setting, and in the absence of other antiviral treatments or progression despite receipt of standard treatments, high-titer CCP from a recently recovered donor is a reasonable approach,” they conclude.
Eileen Barrett, MD, MPH, an assistant professor in the division of hospital medicine at the University of New Mexico in Albuquerque, said in an interview that “clinical guidelines like this really help practicing physicians as we navigate the explosion of research findings since the start of the pandemic.”
One strong recommendation
Dr. Barrett pointed out that four of the five recommendations are rated “weak.”
“The weak recommendations for convalescent plasma in most situations is very humbling,” she said, “particularly as we recall the earliest days of the pandemic when many hospitalized patients received this treatment when little was known about what could help.”
She highlighted the paper’s only strong recommendation, which was against convalescent plasma use for the vast majority of hospitalized patients with COVID.
“That clinical bottom line is what most clinicians will look for,” she said.
“Similarly,” she said, “the accompanying editorial is so helpful in reminding the reader that, despite some possible benefit to convalescent plasma in a smaller subgroup of patients, variant-appropriate monoclonal antibodies and antivirals are better options.”
The disclosures for lead author of the guidelines, Lise J. Estcourt, MB BChir, DPhil, with the National Health Service Blood and Transplant Department and Radcliffe department of medicine at the University of Oxford (England) and her colleagues are available at https://rmed.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1079. The editorialists and Dr. Barrett declare no relevant financial relationships.
FROM ANNALS OF INTERNAL MEDICINE
Blood pressure smartphone app fails to beat standard self-monitoring
Here’s another vote for less screen time.
“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”
While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.
In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.
Methods
Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.
After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.
Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).
“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.
New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”
Findings can likely be extrapolated to other apps
Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.
“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”
Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”
When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”
Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”
To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.
Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
Study limitations
Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.
These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”
Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”
“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.
Here’s another vote for less screen time.
“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”
While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.
In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.
Methods
Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.
After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.
Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).
“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.
New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”
Findings can likely be extrapolated to other apps
Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.
“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”
Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”
When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”
Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”
To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.
Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
Study limitations
Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.
These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”
Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”
“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.
Here’s another vote for less screen time.
“By itself, standard self-measured blood pressure (SMBP) has minimal effect on BP control,” wrote lead author Mark J. Pletcher, MD, of the University of California, San Francisco, and colleagues in JAMA Internal Medicine. “To improve BP control, SMBP must be accompanied by patient feedback, counseling, or other cointerventions, and the BP-lowering effects of SMBP appear to be proportional to the intensity of the cointervention.”
While this is known, higher-intensity cointerventions demand both money and time, prompting development of new devices that link with smartphone apps, they continued.
In the prospective randomized trial, patients with hypertension were randomly assigned to self-measure their blood pressure using a standard device that paired with a connected smartphone application or to self-measure their blood pressure with a standard device alone. Both groups achieved about an 11 mm Hg reduction in systolic BP over 6 months, reported similar levels of satisfaction with the monitoring process, and shared their readings with their physicians with similar frequency.
Methods
Dr. Pletcher and colleagues enrolled 2,101 adults who self-reported a systolic BP greater than 145 mm Hg and expressed a commitment to reduce their BP by at least 10 points in their trial. The participants, who were generally middle-aged or older, were randomized in a 1:1 ratio to monitor their BP using standard SMBP or “enhanced” SMBP. The standard group used the OMRON BP monitor alone, while the enhanced group used the same BP monitor coupled with the OMRON Connect smartphone app.
After 6 months of follow-up for each patient, mean BP reduction from baseline in the standard group was 10.6 mm Hg, compared with 10.7 mm Hg in the enhanced group, a nonsignificant difference (P = .81). While slightly more patients in the enhanced group achieved a BP lower than 140/90 mm Hg (32% vs. 29%; odds ratio, 1.17; 95% confidence interval, 1.01-1.34), this trend did not extend below the 130/80 mm Hg threshold.
Other secondary outcomes were also similar between groups. For example, 70% of participants in the enhanced group said they would recommend their SMBP process to a friend, compared with 69% of participants who followed the standard monitoring approach. The smartphone app had little impact on sharing readings with physicians, either, based on a 44% share rate in the enhanced group versus 48% in the standard group (P = .22).
“Enhanced SMBP does not provide any additional reduction in BP,” the investigators concluded.
New devices that link with smartphone apps, like the one used in this trial, “transmit BP measurements via wireless connection to the patient’s smartphone, where they are processed in a smartphone application to support tracking, visualization, interpretation, reminders to measure BP and/or take medications; recommendations for lifestyle interventions, medication adherence, or to discuss their BP with their clinician; and communications (for example, emailing a summary to a family member or clinician),” the researchers explained. While these devices are “only slightly more expensive than standard SMBP devices,” their relative efficacy over standard SMBP is “unclear.”
Findings can likely be extrapolated to other apps
Although the trial evaluated just one smartphone app, Dr. Pletcher suggested that the findings can likely be extrapolated to other apps.
“Most basic BP-tracking apps have some version or subset of the same essential functionality,” he said, in an interview. “My guess is that apps that meet this description without some substantially different technology or feature would likely show the same basic results as we did.”
Making a similar remark, Matthew Jung, MD, of Keck Medicine of USC, Los Angeles, stated that the findings can be “reasonably extrapolated” to other BP-tracking apps with similar functionality “if we put aside the study’s issues with power.”
When it comes to smartphone apps, active engagement is needed to achieve greater impacts on blood pressure, Dr. Pletcher said, but “there is so much competition for people’s attention on their phone that it is hard to maintain active engagement with any health-related app for long.”
Still, Dr. Pletcher hasn’t given up on biometric apps, noting that “with the right technology and connectivity and user experience (for both patient and clinician), they still could be game-changing for managing chronic conditions like hypertension.”
To this end, he and his colleagues are exploring technologies to passively monitor health-related measurements like BP, potentially sidestepping the pitfall of active engagement.
Dr. Jung said the study is noteworthy for several reasons, including its large size, similar level of comfort with technology reported by both groups, and representation of Black and Hispanic participants, who accounted for almost one-third of the population.
Study limitations
Dr. Jung pointed out several study limitations, including the lack of standardized measurement of BP, which left more than one-third of patients unevaluated via chart review, as well as gaps in usage data, such as that one-third of the participants never confirmed receipt of a device, and less than half of the enhanced group reported using the smartphone application.
These limitations “may have detracted from its ability to identify the true efficacy of an enhanced app-based BP tracking device,” he said. “In contrast, each of these issues also helped us get a better picture for how well these devices may work in the real world.”
Dr. Jung also commented on the duration of the study, noting that only 10 weeks passed, on average, from baseline to follow-up BP measurement, which “may not have been sufficient for a possible difference between enhanced and standard BP monitoring to become noticeable.”
“This may be especially important when taking into consideration the time required to mail the devices out to patients, for patients to become familiar with usage of the devices, and for them to start using the devices in a meaningful way,” he added.
The study was supported the Patient-Centered Outcomes Research Institute, the American Medical Association, and the American Heart Association. The investigators disclosed additional relationships with Pfizer, Bristol Myers Squibb, and Novartis. Dr. Jung, who was not involved in the study, disclosed no relevant conflicts of interest.
FROM JAMA INTERNAL MEDICINE
Poor sleep raises risk for fatty liver disease
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Sleep behaviors, both individually and combined, are associated with an increased risk of developing metabolic dysfunction–associated fatty liver disease (MAFLD), according to a Chinese analysis that suggests the effect may be independent of obesity.
Yan Liu, PhD, from the School of Public Health at Sun Yat-sen University in Guangzhou, China, and colleagues studied data on over 5,000 individuals who self-reported sleep behaviors and underwent liver ultrasound.
, increasing the risk by 37%, 59%, and 17%, respectively, whereas people with both poor nighttime sleep and prolonged daytime napping had the “highest risk for developing fatty liver disease,” said Dr. Liu in a press release.
In contrast, having any of six healthy sleep behaviors decreased the risk by 16% each, and even a “moderate improvement in sleep quality was related to a 29% reduction in the risk for fatty liver disease,” he added.
The research, published online in the Journal of Clinical Endocrinology & Metabolism, also indicated that obesity accounted for only one fifth of the effect of sleep quality on MAFLD risk.
Rise in unhealthy lifestyles leads to increase in MALFD
The authors write that MAFLD is the “leading chronic liver disease worldwide,” affecting around a quarter of the adult population, and may lead to end-stage liver diseases and extrahepatic complications, thus “posing a major health and economic burden.”
Moreover, the disease prevalence is “soaring at an unanticipated rate,” increasing from 18% to 29% in China over the past decade, because of a “rapid rise in unhealthy lifestyles,” the authors note.
Sleep disturbance is increasingly prevalent, “and an emerging contributor to multiple metabolic disorders,” with insomnia and habitual snoring, for example, positively correlated with hypertension, impaired glucose metabolism, and dyslipidemia, report the authors.
However, whether sleep quality, which includes “several metabolic-related sleep behaviors,” constitutes an independent risk for MAFLD “over and above” the effect of obesity remains unclear.
To investigate further, the researchers examined data from the baseline survey of the community-based, prospective South China Cohort study, which was conducted in four regions of Southern China and involved 5,430 individuals aged 30-79 years.
Between March 2018 and October 2019, the participants self-reported sleep behaviors on the Pittsburgh Sleep Quality Index questionnaire and underwent ultrasound examination of the liver.
MAFLD was diagnosed in those with hepatic steatosis and one of the following:
- Overweight/obesity, defined by this study as a body mass index greater than or equal to 23 kg/m2.
- Presence of diabetes.
- Evidence of metabolic dysregulation.
After excluding patients with insufficient data, and those with a history of liver cirrhosis, hepatectomy, or liver cancer, among others, the team included 5,011 individuals with an average age of 64 years and a mean body mass index of 24.31 kg/m2. Forty percent were male.
Obesity was present in 13% of participants, whereas 15% had diabetes, 58% hypertension, and 35% metabolic syndrome.
MAFLD was diagnosed in 28% of the study population. They were older, more likely to be female with a higher education, and had a higher prevalence of preexisting metabolic disorders and worse metabolic profiles, than those without the disease.
Turning to the associations between sleep and the risk of MAFLD, the researchers say that “in contrast to previous reports, neither shorter nor longer sleep duration was found to be associated with the risk for MAFLD.”
However, after adjusting for demographics, lifestyles, medication, and preexisting metabolic comorbidities including hypertension, diabetes, and obesity, they found that the risk of MAFLD was significantly associated with late bedtime (defined as after 10 p.m.), at an odds ratio of 1.37 (P < .05).
MAFLD was also linked to snoring, at an odds ratio of 1.59, and to daytime napping for longer than 30 minutes, at an odds ratio of 1.17 (P < .05 for both).
When the team compared low-risk and high-risk sleep factors, they found that participants who had an early bedtime, slept 7-8 hours per night, never or rarely had insomnia or snoring, had infrequent daytime sleepiness, and daytime napping of half-hour or less had an odds ratio for MAFLD vs. other participants of 0.64 (P < .05).
Combining those factors into a healthy sleep score, the team found that each additional increase of healthy sleep score was associated with a fully adjusted odds ratio for MAFLD of 0.84 (P < .05).
In contrast, individuals with poor nocturnal sleep patterns and prolonged daytime napping had a higher risk for developing MAFLD, compared with those with a healthy nocturnal sleep pattern and daytime napping of half-hour or less, at an odds ratio of 2.38 (P < .05).
Further analysis indicated that individuals with a sedentary lifestyle and central obesity had a higher risk of MAFLD, but that the presence of obesity accounted for only 20.8% of the total effect of sleep quality on the risk of MAFLD.
“Taken together, our results suggests that obesity only partially mediates the effect of overall sleep quality on MAFLD,” the authors write.
“Given that large proportions of subjects suffering from poor sleep quality are underdiagnosed and undertreated, our study calls for more research into this field and strategies to improve sleep quality,” Dr. Liu said.
The study was supported by the “National Key R&D Program” of China, the Fundamental Research Funds for the Central Universities (Sun Yat-sen University), Natural Science Foundation of Guangdong Province, the Key Project of Medicine Discipline of Guangzhou, and Basic Research Project of Key Laboratory of Guangzhou.
The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Liver protein protects against parenteral nutrition liver injury
Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.
Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.
“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”
Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.
The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.
The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.
Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.
On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.
“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.
Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.
The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.
New findings may lead to novel treatments
Parenteral nutrition is a life saver for children and adults with insufficient absorptive capacity of the gastrointestinal tract. Unfortunately, up to two-thirds of patients requiring parenteral nutrition long-term develop liver disease, which can have fatal outcomes. Parenteral nutrition–associated liver disease is characterized by fibrosis and steatosis. While portal inflammation and cholestasis resolve in patients who can be weaned off parenteral nutrition, portal fibrosis and steatosis unfortunately remain in about half of the patients. The development of therapeutic strategies for this condition has thus far been hampered by the fact that the molecular mechanism of parenteral nutrition–associated liver disease was unknown.
This study by Maitiabua and colleagues from Nanjing University Medical School addresses this problem by performing a proteomic and, importantly, phospho-proteomic analysis of liver biopsies from adults treated with parenteral nutrition compared to normally-feeding controls. They discovered that levels of phosphorylated AKT2, the key signaling mediator of insulin in the liver, are increased, while protein levels of the opposing protein phosphatase 2A (PP2A) are decreased in patients receiving parenteral nutrition.
Remarkably, they could reproduce these same pathway changes in a mouse model of parenteral nutrition, which again led to a chronic activation of the insulin signaling pathway, culminating in the phosphorylation of AKT2. They show further that activation of AKT2 inhibits AMPK and alters hepatic lipid metabolism to promote triglyceride accumulation. Using the experimentally tractable mouse model, they demonstrate further that the ablation of a PP2A isoform in the liver is sufficient to cause lipid accumulation and liver injury. Conversely, restoring PP2A expression improved the hepatic phenotype in mice in the parenteral nutrition model. These findings could also be mimicked using pharmacological activation and inhibition of PP2A.
In sum, this experimental study could some day lead the way to novel treatments of parenteral nutrition-induced liver disease through the use of PP2A activators.
Klaus H. Kaestner, PhD, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine,University of Pennsylvania, Philadelphia.
New findings may lead to novel treatments
Parenteral nutrition is a life saver for children and adults with insufficient absorptive capacity of the gastrointestinal tract. Unfortunately, up to two-thirds of patients requiring parenteral nutrition long-term develop liver disease, which can have fatal outcomes. Parenteral nutrition–associated liver disease is characterized by fibrosis and steatosis. While portal inflammation and cholestasis resolve in patients who can be weaned off parenteral nutrition, portal fibrosis and steatosis unfortunately remain in about half of the patients. The development of therapeutic strategies for this condition has thus far been hampered by the fact that the molecular mechanism of parenteral nutrition–associated liver disease was unknown.
This study by Maitiabua and colleagues from Nanjing University Medical School addresses this problem by performing a proteomic and, importantly, phospho-proteomic analysis of liver biopsies from adults treated with parenteral nutrition compared to normally-feeding controls. They discovered that levels of phosphorylated AKT2, the key signaling mediator of insulin in the liver, are increased, while protein levels of the opposing protein phosphatase 2A (PP2A) are decreased in patients receiving parenteral nutrition.
Remarkably, they could reproduce these same pathway changes in a mouse model of parenteral nutrition, which again led to a chronic activation of the insulin signaling pathway, culminating in the phosphorylation of AKT2. They show further that activation of AKT2 inhibits AMPK and alters hepatic lipid metabolism to promote triglyceride accumulation. Using the experimentally tractable mouse model, they demonstrate further that the ablation of a PP2A isoform in the liver is sufficient to cause lipid accumulation and liver injury. Conversely, restoring PP2A expression improved the hepatic phenotype in mice in the parenteral nutrition model. These findings could also be mimicked using pharmacological activation and inhibition of PP2A.
In sum, this experimental study could some day lead the way to novel treatments of parenteral nutrition-induced liver disease through the use of PP2A activators.
Klaus H. Kaestner, PhD, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine,University of Pennsylvania, Philadelphia.
New findings may lead to novel treatments
Parenteral nutrition is a life saver for children and adults with insufficient absorptive capacity of the gastrointestinal tract. Unfortunately, up to two-thirds of patients requiring parenteral nutrition long-term develop liver disease, which can have fatal outcomes. Parenteral nutrition–associated liver disease is characterized by fibrosis and steatosis. While portal inflammation and cholestasis resolve in patients who can be weaned off parenteral nutrition, portal fibrosis and steatosis unfortunately remain in about half of the patients. The development of therapeutic strategies for this condition has thus far been hampered by the fact that the molecular mechanism of parenteral nutrition–associated liver disease was unknown.
This study by Maitiabua and colleagues from Nanjing University Medical School addresses this problem by performing a proteomic and, importantly, phospho-proteomic analysis of liver biopsies from adults treated with parenteral nutrition compared to normally-feeding controls. They discovered that levels of phosphorylated AKT2, the key signaling mediator of insulin in the liver, are increased, while protein levels of the opposing protein phosphatase 2A (PP2A) are decreased in patients receiving parenteral nutrition.
Remarkably, they could reproduce these same pathway changes in a mouse model of parenteral nutrition, which again led to a chronic activation of the insulin signaling pathway, culminating in the phosphorylation of AKT2. They show further that activation of AKT2 inhibits AMPK and alters hepatic lipid metabolism to promote triglyceride accumulation. Using the experimentally tractable mouse model, they demonstrate further that the ablation of a PP2A isoform in the liver is sufficient to cause lipid accumulation and liver injury. Conversely, restoring PP2A expression improved the hepatic phenotype in mice in the parenteral nutrition model. These findings could also be mimicked using pharmacological activation and inhibition of PP2A.
In sum, this experimental study could some day lead the way to novel treatments of parenteral nutrition-induced liver disease through the use of PP2A activators.
Klaus H. Kaestner, PhD, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, Perelman School of Medicine,University of Pennsylvania, Philadelphia.
Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.
Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.
“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”
Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.
The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.
The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.
Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.
On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.
“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.
Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.
The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.
Hepatic protein PP2A-C-alpha may serve as a protective factor against parenteral nutrition–associated hepatic steatosis by improving liver function, according to a recent study published in Cellular and Molecular Gastroenterology and Hepatology.
Parenteral nutrition–associated hepatic steatosis likely involves the down-regulation of hepatic PP2A-C-alpha and consequent increased phosphorylation of Akt2; this in turn alters hepatic lipid metabolism, promotes triglyceride accumulation, and leads to liver injury, wrote the researchers, led by Gulisudumu Maitiabula and Feng Tian of the Research Institute of General Surgery at Jinling Hospital, Nanjing, China, and the Medical School of Nanjing University.
“Our study provides a strong rationale that PP2A-C-alpha may be involved in the pathogenesis of [parenteral nutrition–associated hepatic steatosis],” they wrote. “Further research is merited to establish whether interventions to enhance PP2A function might suppress the development of hepatic steatosis in patients receiving long-term [parenteral nutrition].”
Parenteral nutrition can be a lifesaving therapy for patients with intestinal failure caused by insufficient bowel length or function, the authors noted However, long-term use can lead to potentially fatal complications such as liver disease, but an understanding of the pathological mechanisms behind parenteral nutrition–associated hepatic steatosis limited.
The research team performed comparative proteomic/phosphoproteomic analyses of liver samples from 10 patients with parenteral nutrition–associated hepatic steatosis, as well as 8 cholelithiasis patients as controls, who were admitted to Jinling Hospital between June 2018 and June 2019. The researchers also assessed the effect of PP2A-C-alpha on liver injury from total parenteral nutrition in mice.
The research team found that PP2A-C-alpha was down-regulated in patients and mice with parenteral nutrition–associated hepatic steatosis. In addition, in patients with parenteral nutrition–associated hepatic steatosis, they found enhanced activation of serine/threonine kinase Akt2 and decreased activation of AMPK.
Mice that were given total parenteral nutrition infusion for 14 days developed hepatic steatosis, down-regulation of PP2A-C-alpha, activation of Akt2, and inhibition of AMPK. Hepatocyte-specific deletion of PP2A-C-alpha in mice given parenteral nutrition exacerbated the Akt2 activation, AMPK inhibition, and hepatic steatosis through an effect on fatty acid degradation.
On the other hand, forced expression of PP2A-C-alpha led to reductions in hepatocyte fat deposition and the pathological score for liver steatosis. Overexpression also significantly improved hepatic steatosis, suppressed Akt2, and activated AMPK. In addition, pharmacological activation of Akt2 in mice overexpressing PP2A-C-alpha led to the aggravation of hepatic steatosis.
“Collectively, these observations suggest that [parenteral nutrition] for [more than] 14 days leads to a down-regulation in PP2A-C-alpha expression that activates Akt2-dependent signaling, which would likely lead to hepatic steatosis,” the study authors wrote.
Intervention trials of PP2A-C-alpha in humans have not been performed because PP2A-C-alpha activators or effector analogs were unavailable for clinical use, they wrote. Additional clinical studies are needed to investigate the effects of PP2A-C-alpha intervention on the development of hepatic steatosis in patients receiving long-term parenteral nutrition.
The study was supported by the National Natural Science Foundation of China, the Science Foundation of Outstanding Youth in Jiangsu Province, the National Science and Technology Research Funding for Public Welfare Medical Projects, “The 13th Five-Year Plan” Foundation of Jiangsu Province for Medical Key Talents, and the Natural Science Foundation of Jiangsu Province. The study authors disclosed no conflicts of interest.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY