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Internists’ patient visits rebound to near pre-COVID norms: Pay down slightly from previous year
Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.
The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).
Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.
It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
Half say pay is fair
Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.
Some indicators in the survey responses may help explain the dissatisfaction.
Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.
Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:
- Having so many rules and regulations (24%)
- Having to work long hours (16%)
- Dealing with difficult patients (16%)
- Working with electronic health records systems (11%)
- Danger/risk associated with treating COVID-19 patients (10%)
Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
More than one-third lost income
More than one-third of internists (36%) reported that they lost some income during the past year.
Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.
Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.
“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.
“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”
If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.
But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.
That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.
A version of this article first appeared on Medscape.com.
Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.
The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).
Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.
It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
Half say pay is fair
Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.
Some indicators in the survey responses may help explain the dissatisfaction.
Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.
Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:
- Having so many rules and regulations (24%)
- Having to work long hours (16%)
- Dealing with difficult patients (16%)
- Working with electronic health records systems (11%)
- Danger/risk associated with treating COVID-19 patients (10%)
Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
More than one-third lost income
More than one-third of internists (36%) reported that they lost some income during the past year.
Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.
Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.
“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.
“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”
If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.
But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.
That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.
A version of this article first appeared on Medscape.com.
Internists are seeing only 3% fewer patients than they did before the COVID-19 pandemic (72 per week on average now vs. 74 before the pandemic). Comparatively, for pediatricians, patient volume remains down 18%. Dermatologists, otolaryngologists, and orthopedists report that visits are down by about 15%.
The number of hours worked also rebounded for internists. In fact, some report working slightly more hours now than they did before the pandemic (52 hours a week, up from 50).
Pay for internists continues to hover near the bottom of the scale among specialties. In this year’s Medscape Internist Compensation Report 2021, internists averaged $248,000, down from $251,000 last year. Pediatricians were the lowest paid, at $221,000, followed by family physicians, at $236,000. Plastic surgeons made the most, at $526,000, followed by orthopedists, at $511,000.
It helped to be self-employed. These internists made $276,000 on average, compared with $238,000 for their employed counterparts.
Half say pay is fair
Internists are also near the bottom among specialists who feel they are fairly compensated. As in last year’s survey, just more than half of internists (52%) said they felt that they were fairly paid this year. By comparison, 79% of oncologists reported they were fairly compensated, which is on the high end regarding satisfaction, but only 44% of infectious diseases specialists felt that way.
Some indicators in the survey responses may help explain the dissatisfaction.
Internists are near the top in time spent on paperwork. On average, they spent 19.7 hours on paperwork and administration this year, up slightly from 18.5 last year. Infectious disease physicians spent the most time on those tasks (24.2 hours a week), and anesthesiologists spent the fewest, at 10.1 hours per week.
Administrative work was among many frustrations internists reported. The following are the top five most challenging aspects of the job, according to the respondents:
- Having so many rules and regulations (24%)
- Having to work long hours (16%)
- Dealing with difficult patients (16%)
- Working with electronic health records systems (11%)
- Danger/risk associated with treating COVID-19 patients (10%)
Conversely, the most rewarding aspects were “gratitude/relationships with patients” (31%); “knowing that I’m making the world a better place” (26%); and “being very good at what I do” (20%).
More than one-third lost income
More than one-third of internists (36%) reported that they lost some income during the past year.
Among those who lost income, 81% said they expect income to return to prepandemic levels within 3 years. Half of that group expected the rebound would come within the next year.
Slightly more than one-third of internists said they would participate in the merit-based incentive payment system (MIPS), and 12% said they would participate in advanced alternative payment models. The rest either said they would participate in neither, or they hadn’t decided.
“The stakes for the Quality Payment Program – the program that incorporates MIPS – are high, with a 9% penalty applied to all Medicare reimbursement for failure to participate,” says Elizabeth Woodcock, MBA, CPC, president of the physician practice consulting firm Woodcock and Associates, in Atlanta, Georgia.
“With margins already slim,” she told this news organization, “most physicians can’t afford this massive penalty.”
If they could choose again, most internists (76%) said they would choose medicine, which was almost the same number as physicians overall who would pick medicine again. Oncologists (88%) and ophthalmologists (87%) were the specialists most likely to choose medicine again. Those in physical medicine and rehabilitation were least likely to choose medicine again, at 67%.
But asked about their specialty, internists’ enthusiasm decreased. Only 68% said that they would make that same choice again.
That was up considerably, however, from the 2015 survey: For that year, only 25% said they would choose internal medicine again.
A version of this article first appeared on Medscape.com.
Long-term use of prescription sleep meds unsupported by new research
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
a new study shows.
“While there are good data from [randomized, controlled trials] that these medications improve sleep disturbances in the short term,” few studies have examined whether they provide long-term benefits, stated the authors of the paper, which was published in BMJ Open.
“The current observational study does not support use of sleep medications over the long term, as there were no self-reported differences at 1 or 2 years of follow-up comparing sleep medication users with nonusers,” author Daniel H. Solomon, MD, MPH, from Brigham and Women’s Hospital, Boston, and colleagues wrote.
Women included in the analysis were drawn from the Study of Women’s Health Across the Nation (SWAN), an ongoing multicenter, longitudinal study examining women during the menopausal transition. The average age of the women included in the cohort was 49.5 years and approximately half were White. All women reported a sleep disturbance on at least 3 nights per week during a 2-week interval. At follow up, women were asked to use a Likert scale to rate three aspects of sleep: difficulty initiating sleep, frequent awakening, and waking up early. On the scale, 1 represented having no difficulties on any nights, 3 represented having difficulties 1-2 nights per week, and 5 represented having difficulty 5-7 nights per week.
Women already using prescription sleep medication at their baseline visit were excluded from the study. Medications used included benzodiazepines, selective BZD receptor agonists, and other hypnotics.
Over the 21 years of follow-up in the SWAN study (1995-2016), Dr. Solomon and colleagues identified 238 women using sleep medication and these were compared with a cohort of 447 propensity score–matched non–sleep medication uses. Overall, the 685 women included were similar in characteristics to each other as well as to the other potentially eligible women not included in the analysis.
Sleep disturbance patterns compared
At baseline, sleep disturbance patterns were similar between the two groups. Among medication users, the mean score for difficulty initiating sleep was 2.7 (95% confidence interval, 2.5-2.9), waking frequently 3.8 (95% CI, 3.6-3.9), and waking early 2.9 (95% CI, 2.7-3.1). Among the nonusers, the baseline scores were 2.6 (95% CI, 2.5-2.7), 3.7 (95% CI, 3.6-3.8), and 2.7 (95% CI, 2.5-2.8), respectively. After 1 year, there was no statistically significant difference in scores between the two groups. The average ratings for medication users were 2.6 (95% CI, 2.3-2.8) for difficulty initiating sleep, 3.8 (95% CI, 3.6-4.0) for waking frequently, and 2.8 (95% CI, 2.6-3.0) for waking early.
Average ratings among nonusers were 2.3 (95% CI, 2.2-2.4), 3.5 (95% CI, 3.3-3.6), and 2.5 (95% CI, 2.3-2.6), respectively.
After 2 years, there were still no statistically significant reductions in sleep disturbances among those taking prescription sleep medications, compared with those not taking medication.
The researchers noted that approximately half of the women in this cohort were current or past tobacco users and that 20% were moderate to heavy alcohol users.
More work-up, not more medication, needed
The study authors acknowledged the limitations of an observational study and noted that, since participants only reported medication use and sleep disturbances at annual visits, they did not know whether patients’ medication use was intermittent or of any interim outcomes. Additionally, the authors pointed out that those classified as “nonusers” may have been using over-the-counter medication.
“Investigations should look at detailed-use patterns, on a daily or weekly basis, with frequent outcomes data,” Dr. Solomon said in an interview. “While our data shed new light on chronic use, we only had data collected on an annual basis; daily or weekly data would provide more granular information.”
Regarding clinician prescribing practices, Dr. Solomon said, “short-term, intermittent use can be helpful, but use these agents sparingly” and “educate patients that chronic regular use of medications for sleep is not associated with improvement in sleep disturbances.”
Commenting on the study, Andrea Matsumura, MD, a sleep specialist at the Oregon Clinic in Portland, echoed this sentiment: “When someone says they are having trouble sleeping this is the tip of the iceberg and it warrants an evaluation to determine if someone has a breathing disorder, a circadian disorder, a life situation, or a type of insomnia that is driving the sleeplessness.”
“I think this study supports what we all should know,” Dr. Matsumura concluded. “Sleep aids are not meant to be used long term” and should not be used for longer than 2 weeks without further work-up.
Funding for this study was provided through a grant from the National Institutes of Health. Dr. Solomon has received salary support from research grants to Brigham and Women’s Hospital for unrelated work from AbbVie, Amgen, Corrona, Genentech and Pfizer. The other authors and Dr. Matsumura have reported no relevant financial relationships.
FROM BMJ OPEN
E-cigarettes linked to wheeze, shortness of breath
The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.
Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.
The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.
“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.
“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”
Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.
He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”
The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.
The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.
The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.
A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.
After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.
Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.
“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.
Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.
Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.
The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.
“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.
“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”
Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.
He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”
The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.
The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.
The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.
A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.
After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.
Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.
“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.
Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The use of e-cigarettes is linked to a higher frequency of self-reported wheezing and shortness of breath in adolescents and young adults, according to an online survey. The association was present even after controlling for cigarette and cannabis use.
Previous studies of adolescents and young adults have shown associations between e-cigarette use and wheeze, shortness of breath, and asthma. The Youth Risk Behavior Surveillance (YRBS) survey by the Centers for Disease Control and Prevention and other health agencies, conducted from 2015 to 2017, found that 63.5% of youth who used e-cigarettes also used some combination of cigarettes and cannabis. Combined use was associated with a 55%-65% increased odds of self-reported asthma.
The Population Assessment of Tobacco and Health (PATH) study, which was published in October 2020, had similar findings, though it did not find an association between e-cigarette use alone and wheezing.
“The findings from the current study highlight that we need to keep asking young people about respiratory symptoms, couse of other tobacco products, as well as cannabis use. As more products, including cannabis and various e-cigarette devices, enter the market, assessing respiratory health will be important both where adolescents and young adults receive their health care and in research,” Alayna Tackett, PhD, said in an interview. Dr. Tackett presented the study at the American Thoracic Society’s virtual international conference. She is an assistant professor of preventive medicine at the University of Southern California, Los Angeles.
“I found [the study] very interesting because it seems to be identifying a physiologic response to these e-cigarettes,” said Christopher Pascoe, MD, who was asked to comment. “And they were so young [age 14-21 years]. The fact that these symptoms of wheezing and shortness of breath are coming from people who are this young suggests that there may be chronic problems showing up later with continued use of these devices.”
Dr. Pascoe is an assistant professor of physiology and pathophysiology at the University of Manitoba, Winnipeg, where he also works with the Children’s Hospital Research Institute of Manitoba. His own research examines lung tissue harvested from pneumothorax surgeries in smokers and e-cigarette users to identify markers of inflammation.
He called the research a “good start” at unraveling the impacts of e-cigarettes and smoking, since some people use both products. “The fact that there was still a twofold increase in odds for wheezing, shortness of breath among people who use these e-cigarettes, but weren’t using cannabis and weren’t using cigarettes. I think it’s novel, and it suggests that there is an effect [of e-cigarettes alone].”
The study is based on a self-reported data, which is a significant limitation, especially considering that asthma is often overreported. “Self-report can be fraught with things, but I think it’s an interesting starting point for trying to recruit people who are just e-cigarette users and following them up further,” said Dr. Pascoe.
The researchers surveyed 2,931 individuals aged 14-21 years between Aug. 6 and Aug.30, 2020, with an average age of 18.9 years. Of the respondents, 80% were women and girls, and 75% were White. The high percentage of women and girls was unusual. Dr. Tackett provided no explanation for the atypical demographic but noted that the current study used convenience sampling.
The survey asked about use of e-cigarettes, cigarettes, and cannabis in the past 30 days, as well as asthma diagnosis and respiratory symptoms over the same period. The methodology employed survey management company Lucid, which recruited, collected data from, and provided compensation to participants.
A total of 24% of participants reported asthma, 13% reported wheeze, and 20% reported shortness of breath. Among 1,414 respondents who reported e-cigarette use in the past 30 days, 15% also said they had used cigarettes, and 37% said they had used cannabis.
After controlling for age, birth sex, and race/ethnicity, compared with self-reported never e-cigarette users, there was an association between past 30-day e-cigarette use and self-reported asthma (odds ratio, 1.4; 95% CI, 1.1-1.7), wheeze (OR, 3.1; 95% CI, 2.3-4.2), and shortness of breath (OR, 2.9; 95% CI, 2.3-3.6). After the researchers controlled for past 30-day cigarette cannabis use, the association with asthma was no longer statistically significant (OR, 1.11; 95% CI, 0.87-1.41), but the association with wheeze (OR, 2.3; 95% CI, 1.6-3.0) and shortness of breath (OR, 2.1; 95% CI, 1.6-2.8) remained.
Dr. Tackett noted that wheeze and shortness of breath are only two indicators of respiratory health, and more research needs to be done. Her team is conducting follow-up studies using objective measurement tools such as home-based spirometry in adolescents and young adults who exclusively use e-cigarettes and who have never used e-cigarettes.
“We need to better understand the complex relationships between use of these products and whether multiple product use is associated with worse respiratory outcomes,” said Dr. Tackett.
Dr. Pascoe and Dr. Tackett disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Seaweed and other marine-derived products in skin care, Part II: Cosmetic formulations, fucoidan, and salmon eggs
The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.1-3
In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.4 Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.4 This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.
Recent studies of marine products in cosmetic formulations
In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.5
The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.6
In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).7 Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.7,8
Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.9
Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.10
The skin-lightening potential of fucoidan
In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.11
Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.12
More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.13
In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.14
Salmon eggs
In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.3,15
A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.3,16
In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.1,3,16
More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.3,15
Conclusion
. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].
References
1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.
2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.
3. Nguyen JK et al. J Cosmet Dermatol 2020 Jul;19(7):1555-69.
4. Sanjeewa KKA et al. J Photochem Photobiol B. 2016 Sep;162:100-5.
5. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.
6. Thu NTH et al. J Cosmet Sci. Nov/Dec 2018;69(6):447-62.
7. Jesumani V et al. Mar Drugs. 2019 Dec 6;17(12):688.
8. Kim MS et al. Photochem Photobiol. Jul-Aug 2013;89(4):911-8.
9. Hameury S et al. J Cosmet Dermatol. 2019 Feb;18(1):355-70.
10. Poulose N et al. J Photochem Photobiol B. 2020 Apr;205:111816.
11. Wang ZJ et al. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4);149-55.
12. Jesumani V et al. Int J Biol Macromol. 2019 Nov 1;140:216-24.
13. Jesumani V et al. PLoS One. 2020 Jan 7;15(1):e0227308.
14. Kim JH et al. Mar Drugs. 2017 Oct 20;15(10):321.
15. Lønne GK et al. Int J Cosmet Sci. 2013 Oct;35(5):515-22.
16. Mekas M et al. J Drugs Dermatol. 2015 Nov;14(11):1306-19.
17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.
The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.1-3
In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.4 Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.4 This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.
Recent studies of marine products in cosmetic formulations
In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.5
The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.6
In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).7 Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.7,8
Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.9
Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.10
The skin-lightening potential of fucoidan
In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.11
Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.12
More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.13
In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.14
Salmon eggs
In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.3,15
A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.3,16
In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.1,3,16
More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.3,15
Conclusion
. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].
References
1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.
2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.
3. Nguyen JK et al. J Cosmet Dermatol 2020 Jul;19(7):1555-69.
4. Sanjeewa KKA et al. J Photochem Photobiol B. 2016 Sep;162:100-5.
5. Fabrowska J et al. Acta Pol Pharm. 2017 Mar;74(2):633-41.
6. Thu NTH et al. J Cosmet Sci. Nov/Dec 2018;69(6):447-62.
7. Jesumani V et al. Mar Drugs. 2019 Dec 6;17(12):688.
8. Kim MS et al. Photochem Photobiol. Jul-Aug 2013;89(4):911-8.
9. Hameury S et al. J Cosmet Dermatol. 2019 Feb;18(1):355-70.
10. Poulose N et al. J Photochem Photobiol B. 2020 Apr;205:111816.
11. Wang ZJ et al. Afr J Tradit Complement Altern Med. 2017 Jun 5;14(4);149-55.
12. Jesumani V et al. Int J Biol Macromol. 2019 Nov 1;140:216-24.
13. Jesumani V et al. PLoS One. 2020 Jan 7;15(1):e0227308.
14. Kim JH et al. Mar Drugs. 2017 Oct 20;15(10):321.
15. Lønne GK et al. Int J Cosmet Sci. 2013 Oct;35(5):515-22.
16. Mekas M et al. J Drugs Dermatol. 2015 Nov;14(11):1306-19.
17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.
The use of bioactive ingredients culled from the marine environment has increased significantly in recent years for use in skin care because of the reputed antioxidant and anti-aging activity of these substances.1-3
In the last couple of decades, secondary metabolites with bioactive properties have been identified in seaweeds. Among these substances, phlorotannins have been isolated from brown seaweeds and demonstrated to exhibit anti-allergic, anti-inflammatory, antioxidant, anticancer, and antiwrinkling activity, as well as some capacity to promote hair growth.4 Sanjeewa et al. suggest that phlorotannins, or marine polyphenols, derived from brown seaweed are well suited for use in cosmeceutical formulations and appear to exhibit skin whitening and antiwrinkling properties in particular.4 This column will discuss recent findings regarding the use of marine ingredients in cosmetic formulations, with a particular focus on substances such as fucoidan, as well as emerging evidence regarding the benefits to human skin derived from salmon eggs.
Recent studies of marine products in cosmetic formulations
In 2017, Fabrowska et al. showed in two groups of 10 volunteers each (one ranging from 20 to 30 years old and one from 40 to 50 years old) that the freshwater alga Cladophora glomerate is an effective ingredient for use as a cosmetic agent intended to moisturize and firm the skin.5
The next year, Thu et al. reported on the preparation of a cream mask composed of Vietnamese seaweeds (Caulerpa lentillifera, Sargassum crassifolium, Ulva reticulata, and Kappaphycus alvarezii), which they found to be abundant in proteins, polysaccharides, carotenoids, and other vitamins and to have potent antibacterial, cell proliferation, moisture retention, and tyrosinase inhibitory properties. The authors added that the seaweed cream mask was safe, provoked no irritation, and appeared to be effective in delivering anti-aging and moisturizing benefits.6
In 2019, Jesumani et al., in reviewing the potential cutaneous benefits of bioactive substances in seaweed, noted a significant increase in the use of ingredients found in macroalgae or seaweed in cosmetic formulations, also noting the range of reputed bioactivity (i.e., antioxidant, antitumor, anti-inflammatory, antilipidemic, antimicrobial, and anti-allergic).7 Seaweeds are a significant source of vitamins A, B, C, D, and E, and green, red, and brown algae contain pigments that protect against UV irradiation.7,8
Also that year, Hameury et al. conducted an ex vivo assessment to predict the cutaneous anti-aging benefits of an aqueous gel containing 6.1% marine ingredients (amino acid-enriched giant kelp extract, trace element-enriched seawater, and dedifferentiated sea fennel cells) topically applied on human skin explants. The investigators found that 64 proteins were significantly regulated by the gel when marine ingredients were compared with untreated skin explants, with the ingredients shown to act on the epidermis and dermis. These proteins are involved in multiple functions including gene expression, inflammatory processes, dermal extracellular matrix production, and melanogenesis and keratinocyte proliferation, suggesting, according to the authors, that marine ingredients could play a role in preventing cutaneous aging and contributing to the health of the epidermis and dermis.9
Early in 2020, Poulose et al. reported on the first use of a photoprotective cosmetic cream combining nanomelanin and seaweed that exerts antioxidant, antibacterial, and wound healing activity.10
The skin-lightening potential of fucoidan
In 2017, Wang et al. investigated the antimelanogenic activity of fucoidan – a complex sulfated polysaccharide extracted from brown seaweed known to possess a broad array of biologic functions – on B16 murine melanoma cells. Their in vitro studies revealed that fucoidan suppresses B16 melanoma cell proliferation and cellular tyrosinase activity and has potential as a skin-whitening cosmeceutical agent.11
Two years later, Jesumani et al. investigated the polysaccharides extracted from the seaweed species Sargassum vachellianum, S. horneri, and S. hemiphyllum. Found to be abundant in fucose, all of the evaluated polysaccharides demonstrated dose-dependent antioxidant activity and effectiveness in hindering tyrosinase and elastase. The researchers concluded that all of the tested species display potential as key ingredients in cosmeceutical agents intended to treat wrinkles or lighten skin.12
More recently, a comparative study by the same team revealed that both fucoidan-rich polysaccharide extract and polyphenol-rich extract from the seaweed S. vachellianum delivered significant protective activity. Both protected the skin from UV harm: The fucoidan-rich extract showed superior free radical scavenging and antimicrobial activity, while the polyphenol extract performed better at absorbing UV radiation. The investigators suggested that both extracts could provide a balanced approach to skin protection when featured in skin care products.13
In addition, it is worth noting that a key monomeric component of red macroalgae (Rhodophyta), 3,6-anhydro-l-galactose, has been found in vitro to display skin-whitening activity.14
Salmon eggs
In a 2013 double-blind, randomized clinical trial with 66 patients, Lønne et al. reported that subjects treated topically with salmon egg extract experienced significant amelioration of photoaging, including wrinkles, pigmentation, erythema, and xerosis, yielding global skin appearance improvement.3,15
A pilot study by Mekas et al., which was reported 2 years later and included 75 patients, revealed that skin tone and evenness were improved by a topical exfoliative cream featuring hydrolyzed roe proteins, based on subjective and objective measures comparing 4% glycolic acid.3,16
In 2016, Yoshino et al. showed that human dermal fibroblasts incubated with salmon egg extract upregulated the expression of collagen type I genes and several oxidative genes.3,17 The topical application of hydrolyzed salmon roe proteins to human skin has also been demonstrated to eliminate cell-to-cell adhesions thus ameliorating the appearance of photodamaged skin.1,3,16
More recently, a comprehensive PubMed search on the bioactive ingredients used in Korean cosmeceuticals reported early in 2020 that there is increased interest in salmon eggs because they provide a copious supply of unsaturated fatty acids, proteins, vitamins, and minerals known to nurture cutaneous health.3,15
Conclusion
. Research into the numerous bioactive properties of these multitudinous species has ramped up in recent years and is yielding evidence regarding the efficacy and potential broader uses of such ingredients in cutaneous health care. As we build on our understanding of just how dynamic a source of treatment options may lie under the sea, we become increasingly aware, ironically, of the damage that human industrialization exerts on the planet, as well as these precious marine resources (including the possibly deleterious effects of chemical sunscreens like those that are now banned for sale in Hawai‘i). Humanity will need to become much better stewards of the Earth if we are to enhance our future opportunities and possibly harness the potent marine ingredients still available with the potential to enhance skin health and appearance.
Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].
References
1. Kim SK. J Cosmet Dermatol. 2014;13(1):56-67.
2. Venkatesan J et al. Mar Drugs. 2017;15(5):1-18.
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17. Yoshino A et al. Clin Interv Aging. 2016;11:1159-68.
FIDELIO-DKD: Finerenone cuts new-onset AFib in patients with type 2 diabetes and CKD
Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.
Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.
The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).
The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.
Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.
The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
‘Side benefits can be very helpful’
“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”
Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.
He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.
“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
Hypothesis-generating findings
The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).
The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.
Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.
FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.
Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.
Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.
The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).
The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.
Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.
The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
‘Side benefits can be very helpful’
“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”
Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.
He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.
“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
Hypothesis-generating findings
The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).
The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.
Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.
FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.
Finerenone treatment of patients with type 2 diabetes and diabetic kidney disease was linked to a significant drop in the incidence of new-onset atrial fibrillation as a prespecified, exploratory endpoint of the FIDELIO-DKD pivotal trial that randomized more than 5,700 patients.
Treatment with finerenone linked with a 29% relative reduction compared with placebo in incident cases of atrial fibrillation (AFib), Gerasimos Filippatos, MD, reported at the annual scientific sessions of the American College of Cardiology.
The absolute reduction was modest, a 1.3% reduction from the 4.5% incidence rate on placebo to a 3.2% rate on finerenone during a median 2.6 years of follow-up. Concurrently with the report, the results appeared online (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.079).
The analyses Dr. Filippatos presented also showed that whether or not patients had a history of AFib, there was no impact on either the primary benefit from finerenone treatment seen in FIDELIO-DKD, which was a significant 18% relative risk reduction compared with placebo in the combined rate of kidney failure, a 40% or greater decline from baseline in estimated glomerular filtration rate, or renal death.
Likewise, prior AFib status had no effect on the study’s key secondary endpoint, a significant 14% relative risk reduction in the combined rate of cardiovascular death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure.
The primary results from FIDELIO-DKD (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease) appeared in a 2020 report (N Engl J Med. 2020 Dec 3;383[23];2219-29).
‘Side benefits can be very helpful’
“It’s important to know of finerenone’s benefits beyond the primary outcome of a trial because side benefits can be very helpful,” said Anne B. Curtis, MD, an electrophysiologist and professor and chair of medicine at the University of Buffalo (N.Y.) School of Medicine and Biomedical Sciences. “It’s not a huge benefit, but this could be an added benefit for selected patients,” she said during a press briefing. “Background studies had shown favorable remodeling of the heart [by finerenone] that could affect AFib.”
Possible mitigating effects by finerenone on inflammation and fibrosis might also mediate the drug’s apparent effect on AFib, said Dr. Filippatos, professor of cardiology and director of the Heart Failure and Cardio-Oncology Clinic at Attikon University Hospital and the University of Athens.
He noted that additional data addressing a possible AFib effect of finerenone will emerge soon from the FIGARO-DKD trial, which enrolled patients similar to those in FIDELIO-DKD but with more moderate stages of kidney disease, and from the FINEARTS-HF trial, which is examining the effect of finerenone in patients with heart failure with an ejection fraction of at least 40%.
“Heart failure and AFib go together tightly. It’s worth studying this specifically, so we can see whether there is an impact of finerenone on patients with heart failure who may not necessarily have kidney disease or diabetes,” Dr. Curtis said.
Hypothesis-generating findings
The new findings reported by Dr. Filippatos “should be considered hypothesis generating. Until we have more information, upstream therapies, including mineralocorticoid receptor antagonists [MRAs, the umbrella drug class that includes finerenone], should be used in appropriate patient populations based on defined benefits with the hope they will also reduce the development of AFib and atrial flutter over time,” Gerald V. Naccarelli, MD, and coauthors wrote in an editorial that accompanied the report (J Am Coll Cardiol. 2021 May 17. doi: 10.1016/j.jacc.2021.04.080).
The FIDELIO-DKD trial randomized 5,734 patients at 913 sites in 48 countries, including 461 patients with a history of AFib. The observed link of finerenone treatment with a reduced incidence of AFib appeared consistent regardless of patients’ age, sex, race, their kidney characteristics at baseline, baseline levels of systolic blood pressure, serum potassium, body mass index, A1c, or use of glucose-lowering medications.
Finerenone belongs to a new class of MRAs that have a nonsteroidal structure, in contrast with the MRAs spironolactone and eplerenone. This means that finerenone does not produce steroidal-associated adverse effects linked with certain other MRAs, such as gynecomastia, and may also differ in other actions.
FIDELIO-DKD was sponsored by Bayer, the company developing finerenone. Dr. Filippatos has received lecture fees from or participated in the direction of trials on behalf of Bayer, as well as for Amgen, Boehringer Ingelheim, Medtronic, Novartis, Servier, and Vifor. Dr. Curtis is an adviser to and receives honoraria from St. Jude Medical, and receives honoraria from Medtronic. Dr. Naccarelli has been a consultant to Acesion, ARCA, GlaxoSmithKline, Janssen, Milestone, Omeicos, and Sanofi. His coauthors had no disclosures.
FROM ACC 2021
Dapagliflozin misses as treatment for COVID-19 but leaves intriguing signal for benefit
In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.
Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.
In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.
“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.
At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.
“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.
Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.
DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.
The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.
On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.
Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
Results for two primary endpoints
The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).
The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.
Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).
In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.
In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
Data could fuel related studies
According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.
More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.
“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.
For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.
Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.
Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.
Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.
In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.
Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.
In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.
“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.
At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.
“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.
Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.
DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.
The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.
On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.
Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
Results for two primary endpoints
The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).
The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.
Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).
In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.
In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
Data could fuel related studies
According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.
More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.
“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.
For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.
Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.
Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.
Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.
In patients hospitalized with COVID-19 infection, the sodium-glucose transporter 2 inhibitor dapagliflozin showed a trend for benefit relative to placebo on multiple outcomes, including the primary outcome of time to organ failure or death, according to results from the randomized DARE-19 trial.
Because of the failure to reach statistical significance, these results have no immediate relevance, but the trends support interest in further testing SGLT2 inhibitors in acute diseases posing a high risk for organ failure, according to Mikhail Kosiborod, MD.
In a trial that did not meet its primary endpoint, Dr. Kosiborod acknowledged that positive interpretations are speculative, but he does believe that there is one immediate take-home message.
“Our results do not support discontinuation of SGLT2 inhibitors in the setting of COVID-19 as long as patients are monitored,” said Dr. Kosiborod, director of cardiometabolic research at Saint Luke’s Mid-America Heart Institute, Kansas City, Mo.
At many institutions, it has been common to discontinue SGLT2 inhibitors in patients admitted with COVID-19. One reason was the concern that drugs in this class could exacerbate organ damage, particularly if they were to induced ketoacidosis. However, only 2 (0.003%) of 613 patients treated with dapagliflozin developed ketoacidosis, and the signal for organ protection overall, although not significant, was consistent.
“Numerically, fewer patients treated with dapagliflozin experienced organ failure and death, and this was consistent across systems, including the kidney,” Dr. Kosiborod said in presenting the study at the annual scientific sessions of the American College of Cardiology.
Overall, the study suggests that, in the context of COVID-19, dapagliflozin did not show harm and might have potential benefit, he added.
DARE-19 was rapidly conceived, designed, and implemented during the early stages of the COVID-19 pandemic. Based on prior evidence that SGLT2 inhibitors “favorably affect a number of pathophysiologic pathways disrupted during acute illness” and that drugs in this class have provided organ protection in the context of heart failure, chronic kidney disease, and other cardiometabolic conditions, the study was designed to test the hypothesis that this mechanism might improve outcomes in patients hospitalized with COVID-19, Dr. Kosiborod said.
The entry criteria included confirmed or suspected COVID-19 with an onset of 4 days of fewer and one additional risk factor, such as atherosclerotic cardiovascular disease, hypertension, or type 2 diabetes. Patients with significant renal impairment or a history of diabetic ketoacidosis were excluded.
On top of standard treatments for COVID-19, patients were randomized to 10 mg dapagliflozin or placebo once daily. There were two primary endpoints. That of prevention was time to criteria for respiratory, cardiovascular, or renal organ failure or death. The second primary outcome, for recovery, was a hierarchical composite for four endpoints: death, organ failure, status at 30 days if hospitalized, and time to discharge if this occurred before day 30.
Of the 1,250 patients randomized at 95 sites in seven countries, 617 in the dapagliflozin group and 620 patients in the placebo group completed the study. Baseline characteristics, which included a mean of age of 62 years; types of comorbidities; and types of treatments were similar.
Results for two primary endpoints
The curves for the primary outcome of prevention had already separated by day 3 and continued to widen over the 30 days in which outcomes were compared. At the end of 30 days, 11.2% of the dapagliflozin group and 13.8% of the placebo group had an event. By hazard ratio, dapagliflozin was linked to 20% nonsignificant relative protection from events (hazard ratio, 0.80; 95% confidence interval, 0.58-1.10).
The trend (P = .168) for the primary endpoint for prevention was reflected in the individual components. For dapagliflozin related to placebo, there were generally similar or greater reductions in new or worsening organ failure (HR, 0.80), cardiac decompensation (HR, 0.81), respiratory decompensation (HR, 0.85), and kidney decompensation (HR, 0.65). None were statistically significant, but the confidence intervals were tight with the upper end never exceeding 1.20.
Moreover, the relative risk reduction for all-cause mortality moved in the same direction (HR, 0.77; 95% CI, 0.52-1.16).
In the hierarchical composite endpoint of recovery, there was no significant difference in the time to discharge, but again many recovery metrics numerically favored dapagliflozin with an overall difference producing a statistical trend (P = .14) similar to organ failure events and death.
In safety analyses, dapagliflozin consistently outperformed placebo across a broad array of safety measure, including any severe adverse event (65% vs. 82%), any adverse event with an outcome of death (32% vs. 48%), discontinuation caused by an adverse event (44% vs. 55%), and acute kidney injury (21% vs. 34%).
Data could fuel related studies
According to Ana Barac, MD, PhD, director of the cardio-oncology program in the Medstar Heart and Vascular Institute, Washington, these data are “thought provoking.” Although this was a negative trial, she said that it generates an “exciting hypothesis” about the potential of SGLT2 inhibitors to provide organ protection. She called for studies to pursue this path of research.
More immediately, Dr. Barac agreed that these data argue against stopping SGLT2 inhibitors in patients admitted to a hospital for COVID-19 infection.
“These data show that these drugs are not going to lead to harm, but they might lead to benefit,” she said.
For James Januzzi, MD, a cardiologist at Massachusetts General Hospital and professor of medicine at Harvard Medical School, both in Boston, DARE-19 was perhaps most impressive because of its rigorous design and execution in the midst of a pandemic.
Over the past year, “the medical literature was flooded with grossly underpowered, poorly designed, single-center studies” yielding results that have been hard to interpret, Dr. Januzzi said. Despite the fact that this study failed to confirm its hypothesis, he said the investigators deserve praise for the quality of the work.
Dr. Januzzi also believes the study is not without clinically relevant findings, particularly the fact that dapagliflozin was associated with a lower rate of adverse events than placebo. This, at least, provides reassurance about the safety of this drug in the setting of COVID-19 infection.
Dr. Kosiborod reported financial relationships with more than 10 pharmaceutical companies, including AstraZeneca, which provided funding for DARE-19. Dr. Barac reported financial relationships with Bristol-Myers Squibb and CTI BioPharma. Dr. Januzzi reported financial relationships with Boehringer Ingelheim, GE Healthcare, Johnson & Johnson, Merck, Novartis, Pfizer, and Roche.
FROM ACC 2021
FDA approves new treatment option for rare anemia
A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.
Special concern
Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.
The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.
Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
About the disease
PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.
Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.
A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.
Special concern
Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.
The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.
Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
About the disease
PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.
Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.
A rare, life-threatening anemia now has a new treatment option. The Food and Drug Administration announced the approval of pegcetacoplan (Empaveli) injection to treat adults with paroxysmal nocturnal hemoglobinuria (PNH). Pegcetacoplan is the first PNH treatment that binds to complement protein C3, according to the FDA announcement. Complement protein C3 is a key component of host immunity and defense.
Special concern
Because of the risk of severe side effects, the drug is available only through a restricted program under a risk evaluation and mitigation strategy (REMS). Serious infections can occur in patients taking pegcetacoplan that can become life-threatening or fatal if not treated early. According to the FDA, REMS are designed to reinforce medication use behaviors and actions that support the safe use of that medication, and only a few drugs require a REMS.
The most common other side effects are injection site reactions, diarrhea, abdominal pain, and fatigue.
Pegcetacoplan was approved based upon a study of 80 patients with PNH and anemia who had been taking eculizumab, a previously approved treatment. During 16 weeks of treatment, patients in the pegcetacoplan group had an average increase in their hemoglobin of 2.4 g/dL, while patients in the eculizumab group had an average decrease in their hemoglobin of 1.5 g/dL.
About the disease
PNH is caused by gene mutations that affect red blood cells, causing them to be defective and susceptible to destruction by a patient’s own immune system. Red blood cells in people with these mutations are defective and can be destroyed by the immune system, causing anemia.
Other symptoms include blood clots and destruction of bone marrow. The disease affects 1-1.5 people per million, with diagnosis typically occurring around ages 35-40, and a median survival of only 10 years after diagnosis, according to the FDA.
TMS ‘surprisingly effective’ for resistant depression
Treatment with transcranial magnetic stimulation (TMS) has a robust effect for patients with major depressive disorder (MDD), results from a large registry study show.
From patient self-reports and clinician assessments, investigators found that TMS was “surprisingly effective” and “an eye-opener” for these patients, lead investigator Harold A. Sackeim, PhD, professor of clinical psychology in psychiatry and radiology, Columbia University, New York, told this news organization.
“In a presumably treatment-resistant population, the efficacy compared favorably with virtually all pharmacologic treatments” tested in the studies, said Dr. Sackeim.
He noted that the registry from which the data were obtained “is the largest for any treatment of depression, period.” These positive results suggest TMS should be considered a first-line treatment for MDD, he added.
The study was presented at the virtual American Psychiatric Association 2021 Annual Meeting and was previously published in the Journal of Affective Disorders.
Real-world study
Results of randomized clinical trials have shown that TMS is effective for episodes of MDD. However, the investigators note that there is a need to characterize and identify patient- and treatment-related clinical outcomes.
The study included 5,010 adult patients who had received a primary diagnosis of MDD and were treated at 103 practices in the United States. Participants completed the nine-item Patient Health Questionnaire (PHQ-9) at baseline and at least one other time following a TMS treatment.
The average baseline PHQ-9 score was 19.8, indicating moderate to severe symptoms. This was also reflected in a smaller sample that included Clinical Global Impressions–Severity (CGI-S) ratings by clinicians, mostly psychiatrists.
About two-thirds of the study population were women. The average age was about 50 years. Participants typically received about 30 TMS sessions over 7 to 8 weeks.
TMS targets tissue in the dorsolateral prefrontal cortex. The standard protocol involves administering “fast” or high-frequency (10-Hz) stimulation on the left side. Sometimes, slow-frequency stimulation on the right side is added. About 57% of patients were treated on the left side, and 43% were treated on both sides. Each session involved delivery of about 3,000 pulses.
In the analysis of patient self-reports (PHQ-9), the response rate, which was defined as resolution of 50% or more of symptoms, was from 58% to 69%. The remission rate, defined as becoming asymptomatic or having minimal symptoms, ranged from 28% to 36%.
Results were about 5% higher in the “completer” sample, which included 3,814 patients who received at least 20 treatments and who completed a PHQ-9 assessment at the end the treatment course.
The number of completers in the analysis was “massive,” said Dr. Sackeim. It’s “ten times larger than in any previous TMS study; all randomized trials have a couple of hundred subjects at most, so this is whopping.”
The results provide “a full snapshot” of TMS in the “real-world” community instead of in the “highly controlled” environment of most studies, he added.
Gender differences
The analysis that included CGI-S clinician measures yielded higher outcome estimates – 79% to 83% for the response rate, and 47% to 63% for the remission rate.
Women tended to have better clinical outcomes. “It appears to me that around age 50 is where you see the difference,” said Dr. Sackeim. “Among women, it looks like the older they get, the better the outcome, whereas men are not showing that type of positive aging effect.”
This difference might be due to hormonal changes associated with menopause and the fact that older men with depression may have had a stroke or brain lesion. Dr. Sackeim said he plans to look more closely at outcomes of women in comparison with men.
This, said Dr. Sackeim, illustrates how rapidly the TMS field is evolving.
He noted that researchers are now personalizing the procedure by determining the optimal target for individual patients. Other investigators are testing different protocols.
In the current study, results tended to be better for those who received 4,000 or more pulses, said Dr. Sackeim. “There was an indication of a dose response effect in terms of how many pulses per session,” he said.
The authors note that the study’s PDQ-9 response and remission rates indicate that clinical outcomes are comparable to those of the seven antidepressants studied in Level 2 of the large Sequenced Treatment Alternatives to Relieve Depression (STAR-D) trial.
Initial data for relapse in the study population are “encouraging,” said Dr. Sackeim. “You don’t see the rapid relapse that you do when you discontinue some treatments, for example with ECT [electroconvulsive therapy].”
The “slower onset of action” over the course of several sessions “may induce longer benefit,” he added.
Expanded use warranted?
The intervention proved very safe. Side effects, including headaches, were minimal, and there were “virtually no cognitive effects,” said Dr. Sackeim.
Dr. Sackeim believes TMS, as it has evolved, “is an outstanding option for treatment-resistant depression, and it has a very bright future” and should not be reserved for patients with established treatment-resistant depression (TRD), which is the current U.S. Food and Drug Administration indication.
“Restricting it to TRD in my mind is probably a mistake. Why shouldn’t the patient who is just starting on their course of treatment for depression have this as a nonpharmacological option?” he said.
Limitations of the study included its open-label design and the fact that only patients’ age, gender, outcome scores, and TMS treatment parameters were recorded in the registry. Other clinical characteristics, including medication use, were unknown.
However, it’s presumed that most patients had TRD, because insurance reimbursement for TMS typically requires an extensive history of failed antidepressant treatment.
Commenting on the study for an interview, Mark George, MD, professor, and Layton McCurdy, endowed chair in psychiatry, the Medical University of South Carolina, Charleston, called the remission and response rates “remarkable.”
The study included a “huge sample size” of Americans suffering from depression “who have not responded to talking therapy or medications,” noted Dr. George.
“This real-world study shows how effective, safe, and important TMS is for depressed patients who do not respond to medications,” he said.
Neuronetics supported the NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript. Dr. Sackeim serves as a scientific adviser to LivaNova PLC, MECTA Corporation, and Neuronetics. He receives honoraria and royalties from Elsevier and Oxford University Press. He is the inventor on nonremunerative U.S. patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices; each patent is held by the MECTA Corporation. He is also the originator of magnetic seizure therapy.
A version of this article first appeared on Medscape.com.
Treatment with transcranial magnetic stimulation (TMS) has a robust effect for patients with major depressive disorder (MDD), results from a large registry study show.
From patient self-reports and clinician assessments, investigators found that TMS was “surprisingly effective” and “an eye-opener” for these patients, lead investigator Harold A. Sackeim, PhD, professor of clinical psychology in psychiatry and radiology, Columbia University, New York, told this news organization.
“In a presumably treatment-resistant population, the efficacy compared favorably with virtually all pharmacologic treatments” tested in the studies, said Dr. Sackeim.
He noted that the registry from which the data were obtained “is the largest for any treatment of depression, period.” These positive results suggest TMS should be considered a first-line treatment for MDD, he added.
The study was presented at the virtual American Psychiatric Association 2021 Annual Meeting and was previously published in the Journal of Affective Disorders.
Real-world study
Results of randomized clinical trials have shown that TMS is effective for episodes of MDD. However, the investigators note that there is a need to characterize and identify patient- and treatment-related clinical outcomes.
The study included 5,010 adult patients who had received a primary diagnosis of MDD and were treated at 103 practices in the United States. Participants completed the nine-item Patient Health Questionnaire (PHQ-9) at baseline and at least one other time following a TMS treatment.
The average baseline PHQ-9 score was 19.8, indicating moderate to severe symptoms. This was also reflected in a smaller sample that included Clinical Global Impressions–Severity (CGI-S) ratings by clinicians, mostly psychiatrists.
About two-thirds of the study population were women. The average age was about 50 years. Participants typically received about 30 TMS sessions over 7 to 8 weeks.
TMS targets tissue in the dorsolateral prefrontal cortex. The standard protocol involves administering “fast” or high-frequency (10-Hz) stimulation on the left side. Sometimes, slow-frequency stimulation on the right side is added. About 57% of patients were treated on the left side, and 43% were treated on both sides. Each session involved delivery of about 3,000 pulses.
In the analysis of patient self-reports (PHQ-9), the response rate, which was defined as resolution of 50% or more of symptoms, was from 58% to 69%. The remission rate, defined as becoming asymptomatic or having minimal symptoms, ranged from 28% to 36%.
Results were about 5% higher in the “completer” sample, which included 3,814 patients who received at least 20 treatments and who completed a PHQ-9 assessment at the end the treatment course.
The number of completers in the analysis was “massive,” said Dr. Sackeim. It’s “ten times larger than in any previous TMS study; all randomized trials have a couple of hundred subjects at most, so this is whopping.”
The results provide “a full snapshot” of TMS in the “real-world” community instead of in the “highly controlled” environment of most studies, he added.
Gender differences
The analysis that included CGI-S clinician measures yielded higher outcome estimates – 79% to 83% for the response rate, and 47% to 63% for the remission rate.
Women tended to have better clinical outcomes. “It appears to me that around age 50 is where you see the difference,” said Dr. Sackeim. “Among women, it looks like the older they get, the better the outcome, whereas men are not showing that type of positive aging effect.”
This difference might be due to hormonal changes associated with menopause and the fact that older men with depression may have had a stroke or brain lesion. Dr. Sackeim said he plans to look more closely at outcomes of women in comparison with men.
This, said Dr. Sackeim, illustrates how rapidly the TMS field is evolving.
He noted that researchers are now personalizing the procedure by determining the optimal target for individual patients. Other investigators are testing different protocols.
In the current study, results tended to be better for those who received 4,000 or more pulses, said Dr. Sackeim. “There was an indication of a dose response effect in terms of how many pulses per session,” he said.
The authors note that the study’s PDQ-9 response and remission rates indicate that clinical outcomes are comparable to those of the seven antidepressants studied in Level 2 of the large Sequenced Treatment Alternatives to Relieve Depression (STAR-D) trial.
Initial data for relapse in the study population are “encouraging,” said Dr. Sackeim. “You don’t see the rapid relapse that you do when you discontinue some treatments, for example with ECT [electroconvulsive therapy].”
The “slower onset of action” over the course of several sessions “may induce longer benefit,” he added.
Expanded use warranted?
The intervention proved very safe. Side effects, including headaches, were minimal, and there were “virtually no cognitive effects,” said Dr. Sackeim.
Dr. Sackeim believes TMS, as it has evolved, “is an outstanding option for treatment-resistant depression, and it has a very bright future” and should not be reserved for patients with established treatment-resistant depression (TRD), which is the current U.S. Food and Drug Administration indication.
“Restricting it to TRD in my mind is probably a mistake. Why shouldn’t the patient who is just starting on their course of treatment for depression have this as a nonpharmacological option?” he said.
Limitations of the study included its open-label design and the fact that only patients’ age, gender, outcome scores, and TMS treatment parameters were recorded in the registry. Other clinical characteristics, including medication use, were unknown.
However, it’s presumed that most patients had TRD, because insurance reimbursement for TMS typically requires an extensive history of failed antidepressant treatment.
Commenting on the study for an interview, Mark George, MD, professor, and Layton McCurdy, endowed chair in psychiatry, the Medical University of South Carolina, Charleston, called the remission and response rates “remarkable.”
The study included a “huge sample size” of Americans suffering from depression “who have not responded to talking therapy or medications,” noted Dr. George.
“This real-world study shows how effective, safe, and important TMS is for depressed patients who do not respond to medications,” he said.
Neuronetics supported the NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript. Dr. Sackeim serves as a scientific adviser to LivaNova PLC, MECTA Corporation, and Neuronetics. He receives honoraria and royalties from Elsevier and Oxford University Press. He is the inventor on nonremunerative U.S. patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices; each patent is held by the MECTA Corporation. He is also the originator of magnetic seizure therapy.
A version of this article first appeared on Medscape.com.
Treatment with transcranial magnetic stimulation (TMS) has a robust effect for patients with major depressive disorder (MDD), results from a large registry study show.
From patient self-reports and clinician assessments, investigators found that TMS was “surprisingly effective” and “an eye-opener” for these patients, lead investigator Harold A. Sackeim, PhD, professor of clinical psychology in psychiatry and radiology, Columbia University, New York, told this news organization.
“In a presumably treatment-resistant population, the efficacy compared favorably with virtually all pharmacologic treatments” tested in the studies, said Dr. Sackeim.
He noted that the registry from which the data were obtained “is the largest for any treatment of depression, period.” These positive results suggest TMS should be considered a first-line treatment for MDD, he added.
The study was presented at the virtual American Psychiatric Association 2021 Annual Meeting and was previously published in the Journal of Affective Disorders.
Real-world study
Results of randomized clinical trials have shown that TMS is effective for episodes of MDD. However, the investigators note that there is a need to characterize and identify patient- and treatment-related clinical outcomes.
The study included 5,010 adult patients who had received a primary diagnosis of MDD and were treated at 103 practices in the United States. Participants completed the nine-item Patient Health Questionnaire (PHQ-9) at baseline and at least one other time following a TMS treatment.
The average baseline PHQ-9 score was 19.8, indicating moderate to severe symptoms. This was also reflected in a smaller sample that included Clinical Global Impressions–Severity (CGI-S) ratings by clinicians, mostly psychiatrists.
About two-thirds of the study population were women. The average age was about 50 years. Participants typically received about 30 TMS sessions over 7 to 8 weeks.
TMS targets tissue in the dorsolateral prefrontal cortex. The standard protocol involves administering “fast” or high-frequency (10-Hz) stimulation on the left side. Sometimes, slow-frequency stimulation on the right side is added. About 57% of patients were treated on the left side, and 43% were treated on both sides. Each session involved delivery of about 3,000 pulses.
In the analysis of patient self-reports (PHQ-9), the response rate, which was defined as resolution of 50% or more of symptoms, was from 58% to 69%. The remission rate, defined as becoming asymptomatic or having minimal symptoms, ranged from 28% to 36%.
Results were about 5% higher in the “completer” sample, which included 3,814 patients who received at least 20 treatments and who completed a PHQ-9 assessment at the end the treatment course.
The number of completers in the analysis was “massive,” said Dr. Sackeim. It’s “ten times larger than in any previous TMS study; all randomized trials have a couple of hundred subjects at most, so this is whopping.”
The results provide “a full snapshot” of TMS in the “real-world” community instead of in the “highly controlled” environment of most studies, he added.
Gender differences
The analysis that included CGI-S clinician measures yielded higher outcome estimates – 79% to 83% for the response rate, and 47% to 63% for the remission rate.
Women tended to have better clinical outcomes. “It appears to me that around age 50 is where you see the difference,” said Dr. Sackeim. “Among women, it looks like the older they get, the better the outcome, whereas men are not showing that type of positive aging effect.”
This difference might be due to hormonal changes associated with menopause and the fact that older men with depression may have had a stroke or brain lesion. Dr. Sackeim said he plans to look more closely at outcomes of women in comparison with men.
This, said Dr. Sackeim, illustrates how rapidly the TMS field is evolving.
He noted that researchers are now personalizing the procedure by determining the optimal target for individual patients. Other investigators are testing different protocols.
In the current study, results tended to be better for those who received 4,000 or more pulses, said Dr. Sackeim. “There was an indication of a dose response effect in terms of how many pulses per session,” he said.
The authors note that the study’s PDQ-9 response and remission rates indicate that clinical outcomes are comparable to those of the seven antidepressants studied in Level 2 of the large Sequenced Treatment Alternatives to Relieve Depression (STAR-D) trial.
Initial data for relapse in the study population are “encouraging,” said Dr. Sackeim. “You don’t see the rapid relapse that you do when you discontinue some treatments, for example with ECT [electroconvulsive therapy].”
The “slower onset of action” over the course of several sessions “may induce longer benefit,” he added.
Expanded use warranted?
The intervention proved very safe. Side effects, including headaches, were minimal, and there were “virtually no cognitive effects,” said Dr. Sackeim.
Dr. Sackeim believes TMS, as it has evolved, “is an outstanding option for treatment-resistant depression, and it has a very bright future” and should not be reserved for patients with established treatment-resistant depression (TRD), which is the current U.S. Food and Drug Administration indication.
“Restricting it to TRD in my mind is probably a mistake. Why shouldn’t the patient who is just starting on their course of treatment for depression have this as a nonpharmacological option?” he said.
Limitations of the study included its open-label design and the fact that only patients’ age, gender, outcome scores, and TMS treatment parameters were recorded in the registry. Other clinical characteristics, including medication use, were unknown.
However, it’s presumed that most patients had TRD, because insurance reimbursement for TMS typically requires an extensive history of failed antidepressant treatment.
Commenting on the study for an interview, Mark George, MD, professor, and Layton McCurdy, endowed chair in psychiatry, the Medical University of South Carolina, Charleston, called the remission and response rates “remarkable.”
The study included a “huge sample size” of Americans suffering from depression “who have not responded to talking therapy or medications,” noted Dr. George.
“This real-world study shows how effective, safe, and important TMS is for depressed patients who do not respond to medications,” he said.
Neuronetics supported the NeuroStar Advanced Therapy System Clinical Outcomes Registry, analysis of the registry data, and the drafting of this manuscript. Dr. Sackeim serves as a scientific adviser to LivaNova PLC, MECTA Corporation, and Neuronetics. He receives honoraria and royalties from Elsevier and Oxford University Press. He is the inventor on nonremunerative U.S. patents for Focal Electrically Administered Seizure Therapy (FEAST), titration in the current domain in ECT, and the adjustment of current in ECT devices; each patent is held by the MECTA Corporation. He is also the originator of magnetic seizure therapy.
A version of this article first appeared on Medscape.com.
Infants with UTI do not have an increased risk of bacterial meningitis
The decision to perform a spinal tap procedure in infants to determine whether they have bacterial meningitis should not be guided by abnormal urinalysis results alone, according to new research published in JAMA Network Open.
The findings suggest febrile infants with positive urinalysis results do not have a higher risk of bacterial meningitis than those with negative urinalysis results.
Nearly 1 in 100,000 people are diagnosed with bacterial meningitis in the United States each year, according to Boston Children’s Hospital. Infants have an increased risk for bacterial meningitis, compared with those in other age groups, according to the Centers for Disease Control and Prevention. However, rates of the infectious disease have been declining in the United States since the late 1990s.
Researchers of the current study said published guidelines and quality initiatives recommend performing a lumbar puncture on febrile infants with positive urinalysis results to exclude bacterial meningitis as a cause.
“It really raises the question of should we be doing everything we’re doing?” study author Brett Burstein, MD, PhD, MPH, said in an interview. “What we conclude here is that, contrary to all the published guidelines, this invasive strategy for testing in well-appearing infants should not be guided by the urinalysis results. That’s a major departure.”
The study adds to growing research that questions whether a lumbar puncture in infants with fever and a positive urinalysis results should be routinely required.
“[Our findings] certainly goes against 30 years of clinical decisions, rules, and guidelines,” Dr. Burstein said. “We think they’re very important and they stand to change practice because approximately 500 infants will undergo these invasive procedures to not miss that needle in the haystack.”
Dr. Burstein, a clinician-scientist in pediatric emergency medicine at Montreal Children’s Hospital, led a team of researchers to perform a meta-analysis of 48 studies, including data from more than 25,000 infants.
Researchers found that the prevalence of bacterial meningitis in well-appearing febrile infants aged 29-60 days with a positive urinalysis results was 0.44%, compared with 0.50% of infants with negative urinalysis results.
Instead of relying on urinalysis results alone, Dr. Burstein suggests doctors use other stratifying biomarkers to decide whether they should perform a lumbar puncture.
“If you’ve done blood testing, for example, and your blood test results suggest serious infection, that should guide the decision to go on to invasive testing,” Dr. Burstein said. “You can use your urinary tract infection information in combination now with blood results.”
This means that, if infants have reassuring blood results, despite having a urinary tract infection, they do not need invasive testing, according to Dr. Burstein.
Some of the risks involved with invasive lumbar puncture testing include infection, bleeding, respiratory problems, as well as pain for the infant and parental anxiety.
Paul Aronson, MD, MHS, of Yale University, New Haven, Conn., who was not involved in the study, said in an interview that he has personally moved away from routine lumbar puncture in infants with a positive urinalysis, but added that many doctors have not.
Dr. Aronson said that, although there have been previous studies on this topic, what sets Dr. Burstein’s study apart is the fact that it has a “tightly defined” group of patients, which are infants aged between 29 and 60 days. He also said it is helpful that the study compared the prevalence of meningitis between infants who had positive urinalysis results with those who had negative results.
“The study compared positive urinalyses to negative analyses, which in the meta-analysis form had not been done previously,” Dr. Aronson said. “And so I think this [current study] probably provides some of the strongest evidence.”
No relevant financial relationships were reported.
The decision to perform a spinal tap procedure in infants to determine whether they have bacterial meningitis should not be guided by abnormal urinalysis results alone, according to new research published in JAMA Network Open.
The findings suggest febrile infants with positive urinalysis results do not have a higher risk of bacterial meningitis than those with negative urinalysis results.
Nearly 1 in 100,000 people are diagnosed with bacterial meningitis in the United States each year, according to Boston Children’s Hospital. Infants have an increased risk for bacterial meningitis, compared with those in other age groups, according to the Centers for Disease Control and Prevention. However, rates of the infectious disease have been declining in the United States since the late 1990s.
Researchers of the current study said published guidelines and quality initiatives recommend performing a lumbar puncture on febrile infants with positive urinalysis results to exclude bacterial meningitis as a cause.
“It really raises the question of should we be doing everything we’re doing?” study author Brett Burstein, MD, PhD, MPH, said in an interview. “What we conclude here is that, contrary to all the published guidelines, this invasive strategy for testing in well-appearing infants should not be guided by the urinalysis results. That’s a major departure.”
The study adds to growing research that questions whether a lumbar puncture in infants with fever and a positive urinalysis results should be routinely required.
“[Our findings] certainly goes against 30 years of clinical decisions, rules, and guidelines,” Dr. Burstein said. “We think they’re very important and they stand to change practice because approximately 500 infants will undergo these invasive procedures to not miss that needle in the haystack.”
Dr. Burstein, a clinician-scientist in pediatric emergency medicine at Montreal Children’s Hospital, led a team of researchers to perform a meta-analysis of 48 studies, including data from more than 25,000 infants.
Researchers found that the prevalence of bacterial meningitis in well-appearing febrile infants aged 29-60 days with a positive urinalysis results was 0.44%, compared with 0.50% of infants with negative urinalysis results.
Instead of relying on urinalysis results alone, Dr. Burstein suggests doctors use other stratifying biomarkers to decide whether they should perform a lumbar puncture.
“If you’ve done blood testing, for example, and your blood test results suggest serious infection, that should guide the decision to go on to invasive testing,” Dr. Burstein said. “You can use your urinary tract infection information in combination now with blood results.”
This means that, if infants have reassuring blood results, despite having a urinary tract infection, they do not need invasive testing, according to Dr. Burstein.
Some of the risks involved with invasive lumbar puncture testing include infection, bleeding, respiratory problems, as well as pain for the infant and parental anxiety.
Paul Aronson, MD, MHS, of Yale University, New Haven, Conn., who was not involved in the study, said in an interview that he has personally moved away from routine lumbar puncture in infants with a positive urinalysis, but added that many doctors have not.
Dr. Aronson said that, although there have been previous studies on this topic, what sets Dr. Burstein’s study apart is the fact that it has a “tightly defined” group of patients, which are infants aged between 29 and 60 days. He also said it is helpful that the study compared the prevalence of meningitis between infants who had positive urinalysis results with those who had negative results.
“The study compared positive urinalyses to negative analyses, which in the meta-analysis form had not been done previously,” Dr. Aronson said. “And so I think this [current study] probably provides some of the strongest evidence.”
No relevant financial relationships were reported.
The decision to perform a spinal tap procedure in infants to determine whether they have bacterial meningitis should not be guided by abnormal urinalysis results alone, according to new research published in JAMA Network Open.
The findings suggest febrile infants with positive urinalysis results do not have a higher risk of bacterial meningitis than those with negative urinalysis results.
Nearly 1 in 100,000 people are diagnosed with bacterial meningitis in the United States each year, according to Boston Children’s Hospital. Infants have an increased risk for bacterial meningitis, compared with those in other age groups, according to the Centers for Disease Control and Prevention. However, rates of the infectious disease have been declining in the United States since the late 1990s.
Researchers of the current study said published guidelines and quality initiatives recommend performing a lumbar puncture on febrile infants with positive urinalysis results to exclude bacterial meningitis as a cause.
“It really raises the question of should we be doing everything we’re doing?” study author Brett Burstein, MD, PhD, MPH, said in an interview. “What we conclude here is that, contrary to all the published guidelines, this invasive strategy for testing in well-appearing infants should not be guided by the urinalysis results. That’s a major departure.”
The study adds to growing research that questions whether a lumbar puncture in infants with fever and a positive urinalysis results should be routinely required.
“[Our findings] certainly goes against 30 years of clinical decisions, rules, and guidelines,” Dr. Burstein said. “We think they’re very important and they stand to change practice because approximately 500 infants will undergo these invasive procedures to not miss that needle in the haystack.”
Dr. Burstein, a clinician-scientist in pediatric emergency medicine at Montreal Children’s Hospital, led a team of researchers to perform a meta-analysis of 48 studies, including data from more than 25,000 infants.
Researchers found that the prevalence of bacterial meningitis in well-appearing febrile infants aged 29-60 days with a positive urinalysis results was 0.44%, compared with 0.50% of infants with negative urinalysis results.
Instead of relying on urinalysis results alone, Dr. Burstein suggests doctors use other stratifying biomarkers to decide whether they should perform a lumbar puncture.
“If you’ve done blood testing, for example, and your blood test results suggest serious infection, that should guide the decision to go on to invasive testing,” Dr. Burstein said. “You can use your urinary tract infection information in combination now with blood results.”
This means that, if infants have reassuring blood results, despite having a urinary tract infection, they do not need invasive testing, according to Dr. Burstein.
Some of the risks involved with invasive lumbar puncture testing include infection, bleeding, respiratory problems, as well as pain for the infant and parental anxiety.
Paul Aronson, MD, MHS, of Yale University, New Haven, Conn., who was not involved in the study, said in an interview that he has personally moved away from routine lumbar puncture in infants with a positive urinalysis, but added that many doctors have not.
Dr. Aronson said that, although there have been previous studies on this topic, what sets Dr. Burstein’s study apart is the fact that it has a “tightly defined” group of patients, which are infants aged between 29 and 60 days. He also said it is helpful that the study compared the prevalence of meningitis between infants who had positive urinalysis results with those who had negative results.
“The study compared positive urinalyses to negative analyses, which in the meta-analysis form had not been done previously,” Dr. Aronson said. “And so I think this [current study] probably provides some of the strongest evidence.”
No relevant financial relationships were reported.
FROM JAMA NETWORK OPEN
Clinical Edge Journal Scan Commentary: HCC May 2021
The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.
Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.
The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.
Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.
The next study explored ways to identify patients who have HCC using PIVKA-II (prothrombin induced by vitamin K deficiency/antagonist – II), a promising marker that may be more sensitive/specific than AFP in identifying patients with liver cancer. Feng et al. used enzyme-linked immunosorbent assay (ELISA) to measure serum PIVKA-II levels in 168 patients with HCC, 150 patients with benign liver disease, and 153 healthy controls. Patients with HCC had significantly higher median PIVKA-II levels (181.50 mAu/mL), compared with atients with noncancerous liver disease (28.6 mAU/mL) or healthy controls 21.82 mAU/mL), with p<0.0001. In addition, PIVKA-II was more sensitive (83.9% vs 64.3%) and more specific (91.5% vs 84.7%) than AFP in identifying patients with HCC. When PIVKA-II and AFP were combined, sensitivity (81.95%) and specificity (89.3%) were increased more, suggesting that this combination of markers may be most useful in clinical practice to identify patients who have HCC.
Finally, in patients whose HCC was treated with orthotopic liver transplantation, acute organ rejection was found to be linked to HCC recurrence. Gul-Klein et al. identified 252 patients who underwent liver transplantation for HCC between 2001 and 2015, 91 of whom had confirmed acute rejection, and 47 of whom had recurrent HCC (the median time to HCC recurrence was 20 months). HCC recurrence was identified in 28.6% of patients with acute rejection, and in 13% of patients without acute rejection (p=0.002). Acute rejection within 20 months of liver transplantation was identified as a significant risk factor for HCC recurrence in multivariate analysis (hazard ratio of 2.91). The authors suggested that more intensive monitoring for HCC recurrence may be appropriate for patients who have evidence of acute rejection.