Federal Practitioner

One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.

Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.

From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .

They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”

Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.

“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.

For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..

Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”

The study was independently supported. Dr. Farah reports no relevant financial relationships.

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

One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.

Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.

From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .

They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”

Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.

“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.

For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..

Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”

The study was independently supported. Dr. Farah reports no relevant financial relationships.

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

One day in 2020, Ronda S. Farah, MD, was spending some downtime from her dermatology practice scrolling through social media. When she opened TikTok, she came across something that piqued her interest: A popular content creator was promoting the supplement biotin as a way to grow hair. Dr. Farah was immediately alarmed, because not only was the evidence that biotin increases hair growth shoddy, but the FDA had also warned that biotin supplements may interfere with lab tests for troponin.

Dr. Farah was moved to action and made a brief TikTok stating that use of biotin does not result in hair growth for most patients, which quickly shot up to over half a million views. She was flooded with messages from influencers and people desperate for an answer to their hair growth questions.

From that point on, Dr. Farah was immersed in the world of hairfluencers, the social media personalities who promote hair care trends, which formed the basis of a review, published in the Journal of Cosmetic Dermatology that she conducted with her colleagues at the University of Minnesota, Minneapolis. .

They reviewed five treatments that represent some of the most frequently discussed hair-growth trends on social media: rosemary, onion juice, rice water, castor oil, and aloe vera. For each, they evaluated recommendations on how the treatments were applied, possible harmful effects to the user, claims that weren’t totally based on scientific evidence, and the theoretical mechanism of action. “Overall,” they concluded, “there is little to no literature supporting these social media trends for hair growth.”

Of the five, rosemary, applied to the scalp or hair, has perhaps the most significant research behind it, according to Dr. Farah and coauthors. Methods of applying rosemary described on social media included use of prepackaged oil, boiling fresh rosemary leaves, adding leaves to oils and spraying it on or massaging it on the scalp, applying it in the hair, or using it as a rinse. Dr. Farah noted that the literature supporting the use of rosemary for hair growth does not represent the most robust science; the studies had small sample sizes and used nonstandardized methods of measuring hair growth.

“It didn’t really meet rigorous, strong study methods that a board-certified dermatologist with their expertise would consider a really solid study,” she said.

For the remaining methods, there was little research to support their use for hair growth. A few, the authors pointed out, can cause scalp burns (aloe vera), damage to hair follicles (rice water), contact dermatitis (aloe vera, onion juice), and, in the case of castor oil, hair felting..

Dr. Farah thinks social media can be a great tool to reach patients, but that people should be wary of what kind of information they’re consuming “and need to be aware of who their hairfluencer is,” she said. And, as she and her coauthors wrote: “We call on dermatologists, as hair and scalp disease experts, to serve as authorities on ‘hairfluencer’ trends and appropriately counsel patients.”

The study was independently supported. Dr. Farah reports no relevant financial relationships.

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

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

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.

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.

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

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.

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.

New research provides novel insight into how mindfulness alters pain-related activity in the brain, in findings that point to more targeted pain management.

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.

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.

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.

The Association for the Advancement of Blood and Biotherapies has released clinical practice guidelines for using COVID-19 convalescent plasma (CCP) in hospital and outpatient settings.

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.

The Association for the Advancement of Blood and Biotherapies has released clinical practice guidelines for using COVID-19 convalescent plasma (CCP) in hospital and outpatient settings.

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.

The Association for the Advancement of Blood and Biotherapies has released clinical practice guidelines for using COVID-19 convalescent plasma (CCP) in hospital and outpatient settings.

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.

Here’s another vote for less screen time. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“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. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“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. Using a smartphone application to track blood pressure won’t lead to any greater reduction in BP than self-monitoring the old-fashioned way, a new study finds.

“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.

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.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, 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.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, 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.

Late bedtimes, snoring, and prolonged daytime napping were significantly associated with MAFLD, 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.

Lung cancer has been the leading cause of cancer-related mortality for decades. It is also predicted to remain as the leading cause of cancer-related mortality through 2030.¹ Platinum-based chemotherapy, including carboplatin and paclitaxel, was introduced 3 decades ago and revolutionized the management of advanced non–small cell lung cancer (NSCLC). A more recent advancement has been mutant epidermal growth factor receptor–tyrosine kinase (EGFR-TK) inhibitors.¹ EGFR is a transmembrane protein that functions by transducing essential growth factor signaling from the extracellular milieu to the cell. As 60% of the advanced NSCLC expresses this receptor, blocking the mutant EGFR receptor was a groundbreaking development in the management of advanced NSCLC.² Development of mutant EGFR-TK inhibitors has revolutionized the management of advanced NSCLC. This study was conducted to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced NSCLC.

Methods 

This meta-analysis was conducted according to Cochrane Collaboration guidelines and reported as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The findings are summarized in the PRISMA flow diagram (Figure 1). Two authors (MZ and MM) performed a systematic literature search using databases such as MEDLINE (via PubMed), Embase, and Cochrane Library using the medical search terms and their respective entry words with the following search strategy: safety, “mutant EGFR-TK inhibitors,” advanced, “non–small cell,” “lung cancer,” “adverse effect,” and literature. Additionally, unpublished trials were identified from clinicaltrials.gov, and references of all pertinent articles were also scrutinized to ensure the inclusion of all relevant studies. The search was completed on June 1, 2021, and we only included studies available in English. Two authors (MM and MZ) independently screened the search results in a 2-step process based on predetermined inclusion/exclusion criteria. First, 890 articles were evaluated for relevance on title and abstract level, followed by full-text screening of the final list of 140 articles. Any disagreements were resolved by discussion or third-party review, and a total of 9 articles were included in the study.

The following eligibility criteria were used: original articles reporting adverse effects (AEs) of mutant EGFR-TK inhibitors in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy. All the patients included in the study had an EGFR mutation but randomly assigned to either treatment or control group. All articles with subjective data on mutant EGFR-TK inhibitors AEs in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy were included in the analysis. Only 9 articles qualified the aforementioned selection criteria for eligibility. All qualifying studies were nationwide inpatient or pooled clinical trials data. The reasons for exclusion of the other 71 articles were irrelevant (n = 31), duplicate (n = 13), reviews (n = 14), and poor data reporting (n = 12). Out of the 9 included studies, 9 studies showed correlation of AEs, including rash, diarrhea, nausea, and fatigue. Seven studies showed correlation of AEs including neutropenia, anorexia, and vomiting. Six studies showed correlation of anemia, cough, and stomatitis. Five studies showed correlation of elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and leucopenia. Four studies showed correlation of fever between mutant EGFR-TK inhibitors and platinum-based chemotherapy.

The primary endpoints were reported AEs including rash, diarrhea, elevated ALT, elevated AST, stomatitis, nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever, respectively. Data on baseline characteristics and clinical outcomes were then extracted, and summary tables were created. Summary estimates of the clinical endpoints were then calculated with risk ratio (RR) and 95% confidence intervals (CIs) using the random-effects model. Heterogeneity between studies was examined with the Cochran Q I² statistic which can be defined as low (25% to 50%), moderate (50% to 75%), or high (> 75%). Statistical analysis was performed using Comprehensive Meta-Analysis Software CMA Version 3.0.

Results

A total of 9 studies including 3415 patients (1775 in EGFR-TK inhibitor treatment group while 1640 patients in platinum-based chemotherapy control group) were included in the study. All 9 studies were phase III randomized control clinical trials conducted to compare the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. Mean age was 61 years in both treatment and control groups. Further details on study and participant characteristics and safety profile including AEs are summarized in Tables 1 and 2. No evidence of publication bias was found.

Rash developed in 45.8% of patients in the treatment group receiving mutant EGFR-TK inhibitors vs only 5.6% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 7.38 with the 95% CI noted, which was statistically significant, confirming higher rash event rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 2).

Diarrhea occurred in 33.6% of patients in the mutant EGFR-TK inhibitors treatment group vs 13.5% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 2.63 and 95% CI was noted, which was statistically significant, confirming higher diarrheal rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 3).

Discussion

Despite the advancement in the treatment of metastatic NSCLC, lung cancer stays as most common cause of cancer-related death in North America and European countries, as patients usually have an advanced disease at the time of diagnosis.³ In the past, platinum-based chemotherapy remained the standard of care for most of the patients affected with advanced NSCLC, but the higher recurrence rate and increase in frequency and intensity of AEs with platinum-based chemotherapy led to the development of targeted therapy for NSCLC, one of which includes mutant EGFR-TK inhibitors, including erlotinib, gefitinib, dacomitinib, lapatinib, and osimertinib.⁴

Smoking is the most common reversible risk factor associated with lung cancer. The EURTAC trial was the first perspective study in this regard, which compared safety and efficacy of mutant EGFR-TK inhibitors with platinum-based chemotherapy. Results analyzed in this study were in favor of mutant EGFR-TK inhibitors except in the group of former smokers.⁵ On the contrary, the OPTIMAL trial showed results in favor of mutant EGFR-TK inhibitors both in active and former smokers; this trial also confirmed the efficacy of mutant EGFR-TK inhibitors in European and Asian populations, confirming the rationale for routine testing of EGFR mutation in all the patients being diagnosed with advanced NSCLC.⁶ Similarly, osimertinib is one of the most recent mutant EGFR-TK inhibitors developed for the treatment of advanced NSCLC in patients with EGFR-positive receptors.

According to the FLAURA trial, patients receiving osimertinib showed significantly longer progression-free survival compared with platinum-based chemotherapy and early mutant EGFR-TK inhibitors. Median progression-free survival was noted to be 18.9 months, which showed 54% lower risk of disease progression in the treatment group receiving osimertinib.⁷ The ARCHER study emphasized a significant improvement in overall survival as well as progression-free survival among a patient population receiving dacomitinib compared with platinum-based chemotherapy.^8,9

Being a potent targeted therapy, mutant EGFR-TK inhibitors do come with some AEs including diarrhea, which was seen in 33.6% of the patients receiving mutant EGFR-TK inhibitors in our study vs 53% in the chemotherapy group, as was observed in the study conducted by Pless and colleagues.¹⁰ Similarly, only 16.5% of patients receiving mutant EGFR-TK inhibitors developed nausea compared with 66% being observed in patients receiving chemotherapy. Correspondingly, only a small fraction of patients (9.7%) receiving mutant EGFR-TK inhibitors developed leucopenia, which was 10 times less reported in mutant EGFR-TK inhibitors compared with patients receiving chemotherapy having a percentage of 100%. A similar trend was reported for neutropenia and anemia in mutant EGFR-TK inhibitors with an incidence of 6.1% and 8.7%, compared with the platinum-based chemotherapy group in which the incidence was found to be 80% and 100%, respectively. It was concluded that platinum-based chemotherapy had played a vital role in the treatment of advanced NSCLC but at an expense of serious and severe AEs which led to discontinuation or withdrawal of treatment, leading to relapse and recurrence of lung cancer.^10,11

Zhong and colleagues conducted a phase 2 randomized clinical trial comparing mutant EGFR-TK inhibitors with platinum-based chemotherapy. They concluded that in patients receiving platinum-based chemotherapy, incidence of rash, vomiting, anorexia, neutropenia, and nausea were 29.4%, 47%, 41.2%, 55.8%, and 32.4% compared with 45.8%, 11%, 21.3%, 6.1%, and 16.5%, respectively, reported in patients receiving mutant EGFR-TK inhibitors for their advanced NSCLC.¹²

Another study was conducted in 2019 by Noronha and colleagues to determine the impact of platinum-based chemotherapy combined with gefitinib on patients with advanced NSCLC.¹³ They concluded that 70% of the patients receiving combination treatment developed rash, which was significantly higher compared with 45.8% patients receiving the mutant EGFR-TK inhibitors alone in our study. Also, 56% of patients receiving combination therapy developed diarrhea vs 33.6% of patients receiving mutant EGFR-TK inhibitors only. Similarly, 96% of patients in the combination therapy group developed some degree of anemia compared with only 8.7% patients in the mutant EGFR-TK inhibitors group included in our study. In the same way, neutropenia was observed in 55% of patients receiving combination therapy vs 6.1% in patients receiving mutant EGFR-TK inhibitors solely. They concluded that mutant EGFR-TK inhibitors when combined with platinum-based chemotherapy increase the incidence of AEs of chemotherapy by many folds.^13,14

Kato and colleagues conducted a study to determine the impact on AEs when erlotinib was combined with anti–vascular endothelial growth factor (VEGF) inhibitors like bevacizumab, they stated that 98.7% of patient in combination therapy developed rash, the incidence of which was only 45.8% in patients receiving mutant EGFR-TK inhibitors as was observed in our study. Similar trends were noticed with other AEs, including diarrhea, fatigue, nausea, and elevated liver enzymes.¹⁵

Conclusions

Our study focused on the safety profile of mutant EGFR-TK inhibitors vs platinum-based chemotherapy in the treatment of advanced NSCLC. Mutant EGFR-TK inhibitors are safer than platinum-based chemotherapy when compared for nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever. On the other end, mutant EGFR-TK inhibitors cause slightly higher AEs, including rash, diarrhea, elevated AST and ALT levels, and stomatitis. However, considering that the development of mutant EGFR-TK inhibitors laid a foundation of targeted therapy, we recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. AEs caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until the patient is symptomatic.

Lung cancer has been the leading cause of cancer-related mortality for decades. It is also predicted to remain as the leading cause of cancer-related mortality through 2030.¹ Platinum-based chemotherapy, including carboplatin and paclitaxel, was introduced 3 decades ago and revolutionized the management of advanced non–small cell lung cancer (NSCLC). A more recent advancement has been mutant epidermal growth factor receptor–tyrosine kinase (EGFR-TK) inhibitors.¹ EGFR is a transmembrane protein that functions by transducing essential growth factor signaling from the extracellular milieu to the cell. As 60% of the advanced NSCLC expresses this receptor, blocking the mutant EGFR receptor was a groundbreaking development in the management of advanced NSCLC.² Development of mutant EGFR-TK inhibitors has revolutionized the management of advanced NSCLC. This study was conducted to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced NSCLC.

Methods 

This meta-analysis was conducted according to Cochrane Collaboration guidelines and reported as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The findings are summarized in the PRISMA flow diagram (Figure 1). Two authors (MZ and MM) performed a systematic literature search using databases such as MEDLINE (via PubMed), Embase, and Cochrane Library using the medical search terms and their respective entry words with the following search strategy: safety, “mutant EGFR-TK inhibitors,” advanced, “non–small cell,” “lung cancer,” “adverse effect,” and literature. Additionally, unpublished trials were identified from clinicaltrials.gov, and references of all pertinent articles were also scrutinized to ensure the inclusion of all relevant studies. The search was completed on June 1, 2021, and we only included studies available in English. Two authors (MM and MZ) independently screened the search results in a 2-step process based on predetermined inclusion/exclusion criteria. First, 890 articles were evaluated for relevance on title and abstract level, followed by full-text screening of the final list of 140 articles. Any disagreements were resolved by discussion or third-party review, and a total of 9 articles were included in the study.

The following eligibility criteria were used: original articles reporting adverse effects (AEs) of mutant EGFR-TK inhibitors in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy. All the patients included in the study had an EGFR mutation but randomly assigned to either treatment or control group. All articles with subjective data on mutant EGFR-TK inhibitors AEs in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy were included in the analysis. Only 9 articles qualified the aforementioned selection criteria for eligibility. All qualifying studies were nationwide inpatient or pooled clinical trials data. The reasons for exclusion of the other 71 articles were irrelevant (n = 31), duplicate (n = 13), reviews (n = 14), and poor data reporting (n = 12). Out of the 9 included studies, 9 studies showed correlation of AEs, including rash, diarrhea, nausea, and fatigue. Seven studies showed correlation of AEs including neutropenia, anorexia, and vomiting. Six studies showed correlation of anemia, cough, and stomatitis. Five studies showed correlation of elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and leucopenia. Four studies showed correlation of fever between mutant EGFR-TK inhibitors and platinum-based chemotherapy.

The primary endpoints were reported AEs including rash, diarrhea, elevated ALT, elevated AST, stomatitis, nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever, respectively. Data on baseline characteristics and clinical outcomes were then extracted, and summary tables were created. Summary estimates of the clinical endpoints were then calculated with risk ratio (RR) and 95% confidence intervals (CIs) using the random-effects model. Heterogeneity between studies was examined with the Cochran Q I² statistic which can be defined as low (25% to 50%), moderate (50% to 75%), or high (> 75%). Statistical analysis was performed using Comprehensive Meta-Analysis Software CMA Version 3.0.

Results

A total of 9 studies including 3415 patients (1775 in EGFR-TK inhibitor treatment group while 1640 patients in platinum-based chemotherapy control group) were included in the study. All 9 studies were phase III randomized control clinical trials conducted to compare the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. Mean age was 61 years in both treatment and control groups. Further details on study and participant characteristics and safety profile including AEs are summarized in Tables 1 and 2. No evidence of publication bias was found.

Rash developed in 45.8% of patients in the treatment group receiving mutant EGFR-TK inhibitors vs only 5.6% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 7.38 with the 95% CI noted, which was statistically significant, confirming higher rash event rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 2).

Diarrhea occurred in 33.6% of patients in the mutant EGFR-TK inhibitors treatment group vs 13.5% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 2.63 and 95% CI was noted, which was statistically significant, confirming higher diarrheal rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 3).

Discussion

Despite the advancement in the treatment of metastatic NSCLC, lung cancer stays as most common cause of cancer-related death in North America and European countries, as patients usually have an advanced disease at the time of diagnosis.³ In the past, platinum-based chemotherapy remained the standard of care for most of the patients affected with advanced NSCLC, but the higher recurrence rate and increase in frequency and intensity of AEs with platinum-based chemotherapy led to the development of targeted therapy for NSCLC, one of which includes mutant EGFR-TK inhibitors, including erlotinib, gefitinib, dacomitinib, lapatinib, and osimertinib.⁴

Smoking is the most common reversible risk factor associated with lung cancer. The EURTAC trial was the first perspective study in this regard, which compared safety and efficacy of mutant EGFR-TK inhibitors with platinum-based chemotherapy. Results analyzed in this study were in favor of mutant EGFR-TK inhibitors except in the group of former smokers.⁵ On the contrary, the OPTIMAL trial showed results in favor of mutant EGFR-TK inhibitors both in active and former smokers; this trial also confirmed the efficacy of mutant EGFR-TK inhibitors in European and Asian populations, confirming the rationale for routine testing of EGFR mutation in all the patients being diagnosed with advanced NSCLC.⁶ Similarly, osimertinib is one of the most recent mutant EGFR-TK inhibitors developed for the treatment of advanced NSCLC in patients with EGFR-positive receptors.

According to the FLAURA trial, patients receiving osimertinib showed significantly longer progression-free survival compared with platinum-based chemotherapy and early mutant EGFR-TK inhibitors. Median progression-free survival was noted to be 18.9 months, which showed 54% lower risk of disease progression in the treatment group receiving osimertinib.⁷ The ARCHER study emphasized a significant improvement in overall survival as well as progression-free survival among a patient population receiving dacomitinib compared with platinum-based chemotherapy.^8,9

Being a potent targeted therapy, mutant EGFR-TK inhibitors do come with some AEs including diarrhea, which was seen in 33.6% of the patients receiving mutant EGFR-TK inhibitors in our study vs 53% in the chemotherapy group, as was observed in the study conducted by Pless and colleagues.¹⁰ Similarly, only 16.5% of patients receiving mutant EGFR-TK inhibitors developed nausea compared with 66% being observed in patients receiving chemotherapy. Correspondingly, only a small fraction of patients (9.7%) receiving mutant EGFR-TK inhibitors developed leucopenia, which was 10 times less reported in mutant EGFR-TK inhibitors compared with patients receiving chemotherapy having a percentage of 100%. A similar trend was reported for neutropenia and anemia in mutant EGFR-TK inhibitors with an incidence of 6.1% and 8.7%, compared with the platinum-based chemotherapy group in which the incidence was found to be 80% and 100%, respectively. It was concluded that platinum-based chemotherapy had played a vital role in the treatment of advanced NSCLC but at an expense of serious and severe AEs which led to discontinuation or withdrawal of treatment, leading to relapse and recurrence of lung cancer.^10,11

Zhong and colleagues conducted a phase 2 randomized clinical trial comparing mutant EGFR-TK inhibitors with platinum-based chemotherapy. They concluded that in patients receiving platinum-based chemotherapy, incidence of rash, vomiting, anorexia, neutropenia, and nausea were 29.4%, 47%, 41.2%, 55.8%, and 32.4% compared with 45.8%, 11%, 21.3%, 6.1%, and 16.5%, respectively, reported in patients receiving mutant EGFR-TK inhibitors for their advanced NSCLC.¹²

Another study was conducted in 2019 by Noronha and colleagues to determine the impact of platinum-based chemotherapy combined with gefitinib on patients with advanced NSCLC.¹³ They concluded that 70% of the patients receiving combination treatment developed rash, which was significantly higher compared with 45.8% patients receiving the mutant EGFR-TK inhibitors alone in our study. Also, 56% of patients receiving combination therapy developed diarrhea vs 33.6% of patients receiving mutant EGFR-TK inhibitors only. Similarly, 96% of patients in the combination therapy group developed some degree of anemia compared with only 8.7% patients in the mutant EGFR-TK inhibitors group included in our study. In the same way, neutropenia was observed in 55% of patients receiving combination therapy vs 6.1% in patients receiving mutant EGFR-TK inhibitors solely. They concluded that mutant EGFR-TK inhibitors when combined with platinum-based chemotherapy increase the incidence of AEs of chemotherapy by many folds.^13,14

Kato and colleagues conducted a study to determine the impact on AEs when erlotinib was combined with anti–vascular endothelial growth factor (VEGF) inhibitors like bevacizumab, they stated that 98.7% of patient in combination therapy developed rash, the incidence of which was only 45.8% in patients receiving mutant EGFR-TK inhibitors as was observed in our study. Similar trends were noticed with other AEs, including diarrhea, fatigue, nausea, and elevated liver enzymes.¹⁵

Conclusions

Our study focused on the safety profile of mutant EGFR-TK inhibitors vs platinum-based chemotherapy in the treatment of advanced NSCLC. Mutant EGFR-TK inhibitors are safer than platinum-based chemotherapy when compared for nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever. On the other end, mutant EGFR-TK inhibitors cause slightly higher AEs, including rash, diarrhea, elevated AST and ALT levels, and stomatitis. However, considering that the development of mutant EGFR-TK inhibitors laid a foundation of targeted therapy, we recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. AEs caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until the patient is symptomatic.

Lung cancer has been the leading cause of cancer-related mortality for decades. It is also predicted to remain as the leading cause of cancer-related mortality through 2030.¹ Platinum-based chemotherapy, including carboplatin and paclitaxel, was introduced 3 decades ago and revolutionized the management of advanced non–small cell lung cancer (NSCLC). A more recent advancement has been mutant epidermal growth factor receptor–tyrosine kinase (EGFR-TK) inhibitors.¹ EGFR is a transmembrane protein that functions by transducing essential growth factor signaling from the extracellular milieu to the cell. As 60% of the advanced NSCLC expresses this receptor, blocking the mutant EGFR receptor was a groundbreaking development in the management of advanced NSCLC.² Development of mutant EGFR-TK inhibitors has revolutionized the management of advanced NSCLC. This study was conducted to determine the safety profile of mutant EGFR-TK inhibitors in the management of advanced NSCLC.

Methods 

This meta-analysis was conducted according to Cochrane Collaboration guidelines and reported as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The findings are summarized in the PRISMA flow diagram (Figure 1). Two authors (MZ and MM) performed a systematic literature search using databases such as MEDLINE (via PubMed), Embase, and Cochrane Library using the medical search terms and their respective entry words with the following search strategy: safety, “mutant EGFR-TK inhibitors,” advanced, “non–small cell,” “lung cancer,” “adverse effect,” and literature. Additionally, unpublished trials were identified from clinicaltrials.gov, and references of all pertinent articles were also scrutinized to ensure the inclusion of all relevant studies. The search was completed on June 1, 2021, and we only included studies available in English. Two authors (MM and MZ) independently screened the search results in a 2-step process based on predetermined inclusion/exclusion criteria. First, 890 articles were evaluated for relevance on title and abstract level, followed by full-text screening of the final list of 140 articles. Any disagreements were resolved by discussion or third-party review, and a total of 9 articles were included in the study.

The following eligibility criteria were used: original articles reporting adverse effects (AEs) of mutant EGFR-TK inhibitors in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy. All the patients included in the study had an EGFR mutation but randomly assigned to either treatment or control group. All articles with subjective data on mutant EGFR-TK inhibitors AEs in patients with advanced NSCLC compared with control groups receiving platinum-based chemotherapy were included in the analysis. Only 9 articles qualified the aforementioned selection criteria for eligibility. All qualifying studies were nationwide inpatient or pooled clinical trials data. The reasons for exclusion of the other 71 articles were irrelevant (n = 31), duplicate (n = 13), reviews (n = 14), and poor data reporting (n = 12). Out of the 9 included studies, 9 studies showed correlation of AEs, including rash, diarrhea, nausea, and fatigue. Seven studies showed correlation of AEs including neutropenia, anorexia, and vomiting. Six studies showed correlation of anemia, cough, and stomatitis. Five studies showed correlation of elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and leucopenia. Four studies showed correlation of fever between mutant EGFR-TK inhibitors and platinum-based chemotherapy.

The primary endpoints were reported AEs including rash, diarrhea, elevated ALT, elevated AST, stomatitis, nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever, respectively. Data on baseline characteristics and clinical outcomes were then extracted, and summary tables were created. Summary estimates of the clinical endpoints were then calculated with risk ratio (RR) and 95% confidence intervals (CIs) using the random-effects model. Heterogeneity between studies was examined with the Cochran Q I² statistic which can be defined as low (25% to 50%), moderate (50% to 75%), or high (> 75%). Statistical analysis was performed using Comprehensive Meta-Analysis Software CMA Version 3.0.

Results

A total of 9 studies including 3415 patients (1775 in EGFR-TK inhibitor treatment group while 1640 patients in platinum-based chemotherapy control group) were included in the study. All 9 studies were phase III randomized control clinical trials conducted to compare the safety profile of mutant EGFR-TK inhibitors in patients with advanced NSCLC. Mean age was 61 years in both treatment and control groups. Further details on study and participant characteristics and safety profile including AEs are summarized in Tables 1 and 2. No evidence of publication bias was found.

Rash developed in 45.8% of patients in the treatment group receiving mutant EGFR-TK inhibitors vs only 5.6% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 7.38 with the 95% CI noted, which was statistically significant, confirming higher rash event rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 2).

Diarrhea occurred in 33.6% of patients in the mutant EGFR-TK inhibitors treatment group vs 13.5% of patients in the control group receiving platinum-based chemotherapy. Overall RR of 2.63 and 95% CI was noted, which was statistically significant, confirming higher diarrheal rates in patients receiving EGFR-TK inhibitors for their advanced NSCLC (Figure 3).

Discussion

Despite the advancement in the treatment of metastatic NSCLC, lung cancer stays as most common cause of cancer-related death in North America and European countries, as patients usually have an advanced disease at the time of diagnosis.³ In the past, platinum-based chemotherapy remained the standard of care for most of the patients affected with advanced NSCLC, but the higher recurrence rate and increase in frequency and intensity of AEs with platinum-based chemotherapy led to the development of targeted therapy for NSCLC, one of which includes mutant EGFR-TK inhibitors, including erlotinib, gefitinib, dacomitinib, lapatinib, and osimertinib.⁴

Smoking is the most common reversible risk factor associated with lung cancer. The EURTAC trial was the first perspective study in this regard, which compared safety and efficacy of mutant EGFR-TK inhibitors with platinum-based chemotherapy. Results analyzed in this study were in favor of mutant EGFR-TK inhibitors except in the group of former smokers.⁵ On the contrary, the OPTIMAL trial showed results in favor of mutant EGFR-TK inhibitors both in active and former smokers; this trial also confirmed the efficacy of mutant EGFR-TK inhibitors in European and Asian populations, confirming the rationale for routine testing of EGFR mutation in all the patients being diagnosed with advanced NSCLC.⁶ Similarly, osimertinib is one of the most recent mutant EGFR-TK inhibitors developed for the treatment of advanced NSCLC in patients with EGFR-positive receptors.

According to the FLAURA trial, patients receiving osimertinib showed significantly longer progression-free survival compared with platinum-based chemotherapy and early mutant EGFR-TK inhibitors. Median progression-free survival was noted to be 18.9 months, which showed 54% lower risk of disease progression in the treatment group receiving osimertinib.⁷ The ARCHER study emphasized a significant improvement in overall survival as well as progression-free survival among a patient population receiving dacomitinib compared with platinum-based chemotherapy.^8,9

Being a potent targeted therapy, mutant EGFR-TK inhibitors do come with some AEs including diarrhea, which was seen in 33.6% of the patients receiving mutant EGFR-TK inhibitors in our study vs 53% in the chemotherapy group, as was observed in the study conducted by Pless and colleagues.¹⁰ Similarly, only 16.5% of patients receiving mutant EGFR-TK inhibitors developed nausea compared with 66% being observed in patients receiving chemotherapy. Correspondingly, only a small fraction of patients (9.7%) receiving mutant EGFR-TK inhibitors developed leucopenia, which was 10 times less reported in mutant EGFR-TK inhibitors compared with patients receiving chemotherapy having a percentage of 100%. A similar trend was reported for neutropenia and anemia in mutant EGFR-TK inhibitors with an incidence of 6.1% and 8.7%, compared with the platinum-based chemotherapy group in which the incidence was found to be 80% and 100%, respectively. It was concluded that platinum-based chemotherapy had played a vital role in the treatment of advanced NSCLC but at an expense of serious and severe AEs which led to discontinuation or withdrawal of treatment, leading to relapse and recurrence of lung cancer.^10,11

Zhong and colleagues conducted a phase 2 randomized clinical trial comparing mutant EGFR-TK inhibitors with platinum-based chemotherapy. They concluded that in patients receiving platinum-based chemotherapy, incidence of rash, vomiting, anorexia, neutropenia, and nausea were 29.4%, 47%, 41.2%, 55.8%, and 32.4% compared with 45.8%, 11%, 21.3%, 6.1%, and 16.5%, respectively, reported in patients receiving mutant EGFR-TK inhibitors for their advanced NSCLC.¹²

Another study was conducted in 2019 by Noronha and colleagues to determine the impact of platinum-based chemotherapy combined with gefitinib on patients with advanced NSCLC.¹³ They concluded that 70% of the patients receiving combination treatment developed rash, which was significantly higher compared with 45.8% patients receiving the mutant EGFR-TK inhibitors alone in our study. Also, 56% of patients receiving combination therapy developed diarrhea vs 33.6% of patients receiving mutant EGFR-TK inhibitors only. Similarly, 96% of patients in the combination therapy group developed some degree of anemia compared with only 8.7% patients in the mutant EGFR-TK inhibitors group included in our study. In the same way, neutropenia was observed in 55% of patients receiving combination therapy vs 6.1% in patients receiving mutant EGFR-TK inhibitors solely. They concluded that mutant EGFR-TK inhibitors when combined with platinum-based chemotherapy increase the incidence of AEs of chemotherapy by many folds.^13,14

Kato and colleagues conducted a study to determine the impact on AEs when erlotinib was combined with anti–vascular endothelial growth factor (VEGF) inhibitors like bevacizumab, they stated that 98.7% of patient in combination therapy developed rash, the incidence of which was only 45.8% in patients receiving mutant EGFR-TK inhibitors as was observed in our study. Similar trends were noticed with other AEs, including diarrhea, fatigue, nausea, and elevated liver enzymes.¹⁵

Conclusions

Our study focused on the safety profile of mutant EGFR-TK inhibitors vs platinum-based chemotherapy in the treatment of advanced NSCLC. Mutant EGFR-TK inhibitors are safer than platinum-based chemotherapy when compared for nausea, leucopenia, fatigue, neutropenia, anorexia, anemia, cough, vomiting, and fever. On the other end, mutant EGFR-TK inhibitors cause slightly higher AEs, including rash, diarrhea, elevated AST and ALT levels, and stomatitis. However, considering that the development of mutant EGFR-TK inhibitors laid a foundation of targeted therapy, we recommend continuing using mutant EGFR-TK inhibitors in patients with advanced NSCLC especially in patients having mutant EGFR receptors. AEs caused by mutant EGFR-TK inhibitors are significant but are usually tolerable and can be avoided by reducing the dosage of it with each cycle or by skipping or delaying the dose until the patient is symptomatic.