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Steroid phobia drives weaker prescribing, nonadherence for AD
, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.
Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.
When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.
In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..
The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.
Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.
Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.
“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”
In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.
The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).
Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).
“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.
For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.
Discussing efficacy and safety
Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.
Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.
“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.
The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”
Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.
Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.
, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.
Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.
When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.
In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..
The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.
Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.
Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.
“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”
In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.
The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).
Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).
“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.
For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.
Discussing efficacy and safety
Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.
Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.
“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.
The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”
Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.
Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.
, Nanette B. Silverberg, MD, said at the Revolutionizing Atopic Dermatitis meeting.
Up to 40% of parents of children with chronic AD cite anxiety surrounding corticosteroids, according to Dr. Silverberg, chief of pediatric dermatology at the Mount Sinai Health System, New York.
When the potential for adverse events are explained to parents who are anxious about a drug, “they take it in a different way than other individuals,” noted Dr. Silverberg, clinical professor of pediatrics and dermatology at Icahn School of Medicine at Mount Sinai.
In a systematic review of 16 studies examining topical corticosteroid phobia in AD, published between 1946 and 2016, the prevalence of corticosteroid phobia among patients with AD or their caregivers ranged from 21% to 83.7%, with definitions of phobia that ranged from “concern” to “irrational fear.” In two studies where adherence was evaluated, patients with corticosteroid phobia had a higher rate of partial adherence (49.4%) or nonadherence (14.1%) when compared with patients who didn’t have a phobia of corticosteroids (29.3 % and 9.8%, respectively)..
The source of these fears can be information from friends, relatives, media, the Internet, as well as doctors, Dr. Silverberg noted. “We have to be responsible for providing proper data to these individuals,” she said.
Primary care providers also treat young children with AD differently from older children, when compared with other specialties, according to the results of one study that involved a survey and a retrospective chart review, published in 2020. In the survey, 88% of primary care providers in Chicago said they managed AD differently in children under aged 2 years than in older children, with 65% reporting they were more likely to refer a child under 2 years to a specialist, and 64% said they were less likely to prescribe high-potency topical corticosteroids to children in this age group. The retrospective review found that at PCP visits, significantly more children with AD between aged 2 and 5 years were more likely to be prescribed medium-potency topical corticosteroids (0.66% vs. 0.37%, P < .01) and high-potency topical corticosteroids (0.15% vs. 0.05%; P < .01) than children under 2 years old, respectively.
Of the children who had seen a specialist, more dermatologists (57%) prescribed medium-potency and high-potency topical corticosteroids for children under aged 2 years than did allergists (30%) and pediatricians (15%) (P < .01), according to the study.
“These are our colleagues who are often very strong prescribers using systemic agents, and only 15% of pediatricians will do this,” Dr. Silverberg said. “We’re really looking at a big divide between us and other subspecialties and primary care, and [topical corticosteroids] are frequently underutilized because of these fears.”
In another study looking at the use of topical corticosteroids for AD in the pediatric emergency department (mean age of patients, 6.3 years), from 2012 to 2017, patients at 46 of 167 visits were prescribed over-the-counter topical hydrocortisone, while at 63 of 167 visits, patients were not prescribed or recommended any corticosteroid.
The mean class of the topical corticosteroid prescribed was 5.5, and the most commonly recommended corticosteroid was class 7 (the least potent available) in 61 of 104 patients (P < .001). A dermatologist was consulted in 14 of 167 visits (8.6%), and in those cases, topical corticosteroids were often prescribed (P = .018), as was a higher class of corticosteroids (a mean of 3.1 vs. 5.9; P < .001).
Topical corticosteroids also tend to be prescribed less by internal medicine physicians than by family medicine physicians or dermatologists. A 2020 study of ambulatory care data in the United States from 2006 to 2016 found that internists were 22 times less likely to prescribe topical corticosteroids for AD compared with dermatologists (5.1% vs. 52.2%; P = .001). But there was no significant difference in prescribing between family medicine physicians and dermatologists (39.1% vs. 52.2%, P = .27).
“We know they [corticosteroids] work, but so many people are fearful of them ... even with a low, low side effect profile,” Dr. Silverberg said.
For children with AD, corticosteroid use is “suboptimal” across the United States, with evidence that Medicaid-insured pediatric patients with AD are less likely to see a specialist and less likely to be prescribed high-potency topical corticosteroids compared with commercially-insured patients.
Discussing efficacy and safety
Dr. Silverberg said providers who care for children with AD should talk about the fear surrounding these medications and educate parents with anxiety surrounding corticosteroids. “Side effects are usually short term and limited, so we really can assure parents that there is a long safety profile,” she said.
Asked to comment on this topic, Adelaide Hebert, MD, professor of dermatology and director of pediatric dermatology at the University of Texas, Houston, said that she often sees concerns surrounding the use of topical corticosteroids, both in her practice with parents and when teaching residents in other disciplines, such as pediatrics, family medicine, and emergency medicine.
“We don’t do a good job in medical school educating the students about the safety, applicability, and proper use of topical steroids, and I think that leads to some of the confusion when it comes to properly using this class of medications in treating atopic dermatitis,” she said in an interview.
The use of a high-potency topical steroid is important, she noted, as lower doses may not adequately control AD. “If the patient has very mild disease, this may be just fine,” she noted. Those patients often do not see a pediatric dermatologist, “but the ones with moderate or severe atopic dermatitis often do, and I would say [the problem of] undertreatment is all too common.”
Like Dr. Silverberg, Dr. Hebert said that in her clinical experience, side effects from topical corticosteroids have been rare. “I could count on one hand the number of patients in a 38-year pediatric dermatology practice where they had an adverse effect from a topical steroid,” she said.
Dr. Silverberg reports receiving consulting fees from Amryt Pharma, Galderma, Incyte, and Vyne; non-CME related fees from Pfizer and Regeneron; and contracted research fees from Incyte and the Vitiligo Research Foundation. Dr. Hebert reports receiving research funds from GSK, Leo, Ortho Dermatologics, Galderma, Dermavant, Pfizer, and Arcutis Biotherapeutics paid to her institution; honoraria from Pfizer, Arcutis, Incyte; and having served on the data safety monitoring board for Regeneron-Sanofi, GSK, and Ortho Dermatologics.
FROM RAD 2022
Flu vaccine linked to lower risk for stroke: INTERSTROKE
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
in a large new case-control study.
“While influenza vaccination is a cost-effective method to prevent influenza, it is also an effective way to reduce the burden of stroke,” said study author Christopher Schwarzbach, MD, of Ludwigshafen (Germany) Hospital.
“Our results therefore encourage the wider use of influenza vaccination,” he concluded.
Dr. Schwarzbach presented these data from the INTERSTROKE study at the 2022 European Stroke Organisation Conference.
He explained that acute inflammatory disease is thought to increase the risk for cerebrovascular events, and the seasonality of influenza-like illness appears to be associated with the seasonality of cardiovascular and cerebrovascular events. Previous observational studies have also shown a link between influenza vaccination and a reduced risk for stroke.
The current INTERSTROKE study was a large international case-control study conducted between 2007 and 2015 that involved 13,447 cases (patients within 5 days of their first stroke) and a similar number of age- and gender-matched people from 32 countries across the world.
All cases and control subjects were systematically asked whether they had acute febrile illness in the previous 4 weeks and whether they had received an influenza vaccination within the previous year.
Conditional logistical regression was used to quantify the results, with adjustment for 13 different possible confounding factors, including hypertension, activity, smoking, cardiovascular risk factors, and socioeconomic factors.
Results showed that having had an acute febrile illness in the previous 4 weeks was more commonly reported in the patients with an acute ischemic stroke (8.7%) than in control patients (5.6%). After adjustment for confounding factors, this gives an adjusted risk ratio of 1.18, which was of borderline statistical significance (95% confidence limits, 1.01-1.39), Dr. Schwarzbach reported.
The association between recent febrile illness and acute ischemic stroke was stronger when compared with community control subjects (adjusted odds ratio, 2.0), but it was absent when compared with hospital control subjects.
The association was also only apparent in Australia, China, North America, and Western Europe; it was not seen in other parts of the world.
There was no association between acute febrile illness and acute cerebral hemorrhage.
Flu vaccine linked to halving of stroke risk
Having received a flu vaccine in the previous year was strongly associated with a lower risk for any type of stroke (aOR, 0.53), ischemic stroke (aOR, 0.57), and hemorrhagic stroke (aOR, 0.34).
Dr. Schwarzbach noted that these results were also consistent in an extended statistical model that included variables that might reflect a willingness to be vaccinated and when compared with both community and hospital-based control subjects.
The strength of the association between influenza vaccination and reduced risk for stroke was similar when compared with either community or hospital control subjects, and was only moderately stronger during than outside the influenza season.
The association was also seen in all regions of the world apart from Africa and South Asia, Dr. Schwarzbach reported, but he noted that vaccination rates in these two regions were extremely low.
The researchers also found that the magnitude of the associations between flu vaccination and lower risk for stroke were stronger in individuals who had multiple annual vaccinations, with an odds ratio of 0.54 in those who had received a vaccine every year for the previous 5 years, and of 0.79 in those who had received one to four vaccinations in the previous 5 years.
Mechanism: Immune stimulation?
Discussing possible mechanisms behind these results, Dr. Schwarzbach noted that the finding that the association with influenza vaccination and reduced stroke risk was independent of seasonality was surprising. “We had expected the protective effect of vaccination to be bigger during the influenza season, but this wasn’t the case.”
He suggested that one explanation might be the inclusion of regions of the world where this seasonality doesn’t exist.
But he pointed out that the finding of a stronger association between flu vaccination and lower stroke risk in those who had received more vaccinations has given rise to another theory: that it is the stimulation of the immune system rather than the protection of infection against influenza that is the key factor.
In an interview with Dr. Schwarzbach, Guillaume Turk, MD, professor of neurology at GHU Paris, pointed out that causal inferences are always difficult in case-control studies and in clinical epidemiology in general.
“What makes you think that this association between influenza vaccination and decreased risk is causal rather than due to unmeasured confounders? For example, patients who received vaccination may have received more medical attention and may have been more aware of the risk factors for stroke,” he asked.
Dr. Schwarzbach replied: “Yes, this is the issue of healthy user bias, which is always a problem in this type of research and is hard to address.”
“What we tried to do here is to adjust for variables that might influence the willingness of people to get vaccinated,” he added. “These were mainly socioeconomic factors. But, of course, this is something that we can’t rule out.”
Dr. Schwarzbach noted that, for more reliable information on this association, prospective studies are needed.
‘A plausible effect’
Discussing the study after the presentation, William Whiteley, BM, PhD, a clinical epidemiologist at the University of Edinburgh and a consultant neurologist in NHS Lothian, said vaccination was a potentially important way to reduce stroke.
“In this study, there was a plausible effect on reducing stroke incidence from vaccination against influenza, and also a plausible increase in the risk of stroke from having a recent febrile illness, which we have seen in other studies,” he commented.
Dr. Whiteley noted that this observation was particularly relevant now because of the COVID-19 pandemic.
“We’ve all been worried about the risk of heart attack and stroke after COVID, where we’ve seen quite early high risks, and we are also optimistic about the effect of vaccination on reducing those incidences. We’ve seen data from the U.K. that there may be around a 20% reduction in risk of stroke from vaccination. So, it’s all quite plausible, but at the moment it’s all based on observational evidence and we really need some randomized evidence,” he said.
“Vaccination and infections have all sorts of odd confounders,” he added. “People who get vaccines tend to be more healthy than those who don’t get vaccines, so you can start to see quite implausible effects of vaccination on overall mortality, which probably aren’t real, and you probably can’t get rid of that totally with statistical methods.”
Alastair Webb, MD, University of Oxford (England), asked how reliable the current findings were, given that the occurrence of febrile illnesses and receipt of vaccines were all self-reported, and although there was an association for ischemic stroke and febrile illness, this seemed to go in the opposite direction for hemorrhagic stroke. He also noted that the 50% reduction in stroke risk with vaccination in this study seemed “quite a large magnitude of effect.”
Dr. Whiteley replied: “Yes, it is large, but it is promising.” He cited a previous meta-analysis of randomized studies that showed a roughly 25%-35% reduction in vascular events after flu vaccination, but noted that there was a lot of heterogeneity between studies.
“I’m not sure we’re going to see much more randomized evidence, but I think we can probably all agree that having a vaccine against flu or COVID is a good thing for all of us,” Dr. Whiteley concluded.
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Vastra Gotaland (Sweden), AstraZeneca, Boehringer Ingelheim, Pfizer, MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network. The authors reported no relevant disclosures.
A version of this article first appeared on Medscape.com.
U.S. docs at double the risk of postpartum depression
One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.
“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.
For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”
The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.
Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.
Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
Guilt a driver
Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).
“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.
Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.
Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.
Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.
“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.
However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.
“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”
No relevant financial relationships have been reported.
A version of this article first appeared on Medscape.com.
One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.
“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.
For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”
The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.
Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.
Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
Guilt a driver
Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).
“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.
Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.
Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.
Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.
“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.
However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.
“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”
No relevant financial relationships have been reported.
A version of this article first appeared on Medscape.com.
One in four new mothers who are physicians report experiencing postpartum depression, a rate twice that of the general population, according to new survey findings presented at the American College of Obstetricians and Gynecologists (ACOG) 2022 Annual Meeting.
The survey results weren’t all grim. More than three-fourths (78%) of new mothers reported meeting their own breastfeeding goals. Still, Alison Stuebe, MD, director of maternal-fetal medicine, University of North Carolina School of Medicine, Chapel Hill, said the high postpartum depression rates among physicians might be associated with worse patient care.
“Physicians who have had postpartum depression and provide clinical care for children and birthing people can bring their negative experiences to their clinical work, potentially impacting how they counsel and support their patients,” Dr. Stuebe, who was not involved in the study, told this news organization.
For the study, Emily Eischen, a fourth-year medical student at the University of South Florida Morsani College of Medicine, Tampa, and her colleagues sought to learn how physicians and physician trainee mothers fared in the face of the unique stressors of their jobs, including “strenuous work hours, pressures to get back to work, and limited maternity leave.”
The researchers recruited 637 physicians and medical students with a singleton pregnancy to respond to a survey adapted largely from the U.S. Centers for Disease Control and Prevention’s Infant Feeding Practices Study and the CDC’s Pregnancy Risk Assessment Monitoring System.
Most of the respondents, who were enrolled through social media physician groups and email list-serves, were married non-Hispanic White persons; 71% were practicing or training in pediatrics, family medicine, or obstetrics/gynecology, and 2% were medical students.
Data showed that 25% of participants reported postpartum depression. The highest rates were seen among Hispanic/Latino respondents (31%), Black persons (30%), and non-Hispanic White persons (25%). The lowest rates of postpartum depression were for respondents identifying as Asian (15%).
Guilt a driver
Most respondents (80%) with symptoms of postpartum depression attributed their condition to sleep deprivation. Other frequently cited reasons were problems related to infant feeding (44%), lack of adequate maternity leave (41%), and lack of support at work (33%).
“Feeling guilty for not fulfilling work responsibilities, especially for residents, who are in the most difficult time in their careers and have to hand the workload off to others, can be very stressful,” Ms. Eischen said.
Despite the high rates of postpartum depression in the survey, the investigators found that 99% of respondents had initiated breastfeeding, 72% were exclusively breastfeeding, and 78% said they were meeting their personal breastfeeding goals. All of those rates are higher than what is seen in the general population.
Rates of self-reported postpartum depression were higher among those who did not meet their breastfeeding goals than among those who did (36% vs. 23%; P = .003), the researchers found.
Adetola Louis-Jacques, MD, an assistant professor of medicine, USF Health Obstetrics and Gynecology, and the senior author of the study, said the high breastfeeding rates can be attributed partly to an increased appreciation among physicians that lactation and breastfeeding have proven benefits for women and infant health.
“We still have work to do, but at least the journey has started in supporting birthing and lactating physicians,” she said.
However, Dr. Stuebe wondered whether the survey captured a group of respondents more likely to meet breastfeeding goals. She said she was surprised by the high proportion of respondents who did so.
“When surveys are distributed via social media, we don’t have a clear sense of who chooses to participate and who opts out,” she said in an interview. “If the survey was shared through social media groups that focus on supporting breastfeeding among physicians, it could have affected the results.”
No relevant financial relationships have been reported.
A version of this article first appeared on Medscape.com.
Study: No more autopilot opioids after cesarean delivery
A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.
In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.
The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.
“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.
For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.
With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.
They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.
Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.
Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.
With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.
She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
Potential for ‘huge’ benefit
Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.
“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”
Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.
Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.
In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.
The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.
“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.
For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.
With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.
They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.
Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.
Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.
With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.
She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
Potential for ‘huge’ benefit
Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.
“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”
Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.
Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
A group of clinicians is hoping to prompt a rethink of how opioids are prescribed to new mothers after cesarean deliveries after finding that sending patients home with smaller prescriptions led to dramatic drops in use of the drugs.
In research scheduled to be presented at the annual meeting of the American College of Obstetricians and Gynecologists (ACOG) in San Diego, women undergoing cesarean delivery were randomly assigned to receive prescriptions for either 10 or 20 oxycodone tablets at discharge. Interim data revealed that not only did 10-tablet prescriptions correlate with significantly less opioid consumption, but 35% of all women left their opioid scripts unfilled.
The results suggest physicians should stop “automatically prescribing opioids for caesarean section patients at discharge and, instead, work on individualized prescribing,” said Amanda Selk, MD, associate professor of obstetrics and gynecology at the University of Toronto, who was not involved with the study.
“We need to move away from a culture that says a patient can’t be discharged without an opioid prescription,” Dr. Selk said in an interview.
For the study, researchers at Virginia Tech Carilion School of Medicine, Roanoke, Virginia, set out to understand how discharge opioid prescription sizes impact opioid consumption in women who undergo caesarean delivery. Other specialties have found a correlation between the two.
With “no standard dose recommendation for physicians to follow when it came to prescribing opioids for post-cesarean pain management,” they also wanted to help their own clinicians optimize their prescribing, co-investigator Jaclyn Nunziato, MD, assistant professor of obstetrics and gynecology at Virginia Tech Carilion, told this news organization.
They randomly assigned 134 women undergoing a scheduled cesarean delivery to receive a prescription for 10 or 20 tablets of 5 mg oxycodone at discharge. Most women had one or more previous cesarean deliveries, and none had used opioids in the previous 30 days.
Data from 97 patients presented at the ACOG meeting showed that 35% of women had not filled their opioid prescriptions 6 weeks after surgery. For those who did fill the orders, the average consumption at week 6 of the study was 6.6 tablets in the 10-tablet group and 13.3 tablets in the 20-tablet group (P = .0005), according to the researchers. No patients in either group had requested a refill of their opioid medication.
Despite differences in opioid use, both groups reported similar pain scores throughout the study period, and almost all patients in both groups said they were satisfied with their pain management, the investigators reported.
With an average of 9.2 tablets consumed in the two groups combined, the findings indicate “a standard prescription of 10 tablets may be adequate to manage most patients’ postoperative pain,” Dr. Nunziato said.
She said she hoped the results help change how physicians view the treatment of post-cesarean pain and also help “break down the stigma that opioids are the best treatment option for patients.”
Potential for ‘huge’ benefit
Given the number of cesarean deliveries performed every year in the United States – more than 1.1 million in 2020, according to the U.S. Centers for Disease Control and Prevention – providing smaller post-cesarean opioid prescriptions would be “hugely beneficial to individual patients and our larger community,” said Robyn Goodrich, a medical student at Virginia Tech and the first author of the study.
“The patient would receive an amount that is adequate for controlling their pain and keeping them comfortable but does not put them at risk of developing tolerance and addiction,” she added. “For the community, it reduces the number of prescription opioids that are left over and may be diverted or misused if not properly disposed of.”
Dr. Selk pointed to her own group’s randomized controlled trial, showing that post-cesarean patients who do not receive opioids for pain while in the hospital also do not ask for opioid prescriptions after discharge and that their pain can be well-managed with acetaminophen and nonsteroidal anti-inflammatory drugs.
Dr. Selk, Dr. Nunziato, and Ms. Goodrich have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM ACOG 2022
Longer use of proton pump inhibitors tied to diabetes risk
Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.
The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.
The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.
“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”
If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
Not enough data to support a change in practice
The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.
“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.
“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.
“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”
First-choice therapy for acid-related disorders
PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.
However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.
To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.
Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).
The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.
Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.
Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.
Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).
The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.
Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.
The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.
The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.
The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.
“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”
If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
Not enough data to support a change in practice
The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.
“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.
“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.
“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”
First-choice therapy for acid-related disorders
PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.
However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.
To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.
Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).
The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.
Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.
Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.
Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).
The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.
Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.
The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Long-term use of a proton-pump inhibitor (PPI) was associated with an increased risk of being diagnosed with type 2 diabetes in a large, population-based case-control study in Italy.
The risk of diabetes increased from 19% to 56% as treatment duration increased from 8 weeks to more than 2 years, and prolonged treatment was associated with an even higher risk of diabetes in the youngest patients (age 40-65) and those with the most comorbidities.
The results suggest that “physicians should therefore avoid unnecessary prescription of this class of drugs, particularly for long-term use,” say Stefano Ciardullo, MD, University of Milano-Bicocca, Italy, and colleagues, in their article recently published online in the Journal of Clinical Endocrinology & Metabolism.
“Nonetheless, epidemiologic evidence on the topic remains conflicting,” they acknowledge, adding that “future studies are still needed to validate our findings.”
If the results are confirmed, these “may have important implications for both public health and clinical practice, given the high number of patients being treated with PPIs and the influence of diabetes on morbidity and mortality related to its possible micro- and macrovascular complications,” Dr. Ciardullo and colleagues conclude.
Not enough data to support a change in practice
The current findings align with a recent analysis of three prospective cohort studies of U.S. health care workers that showed a progressively increased risk of diabetes with longer treatment with PPIs, David A. Leiman, MD, MSHP, who was not involved with the current study, told this news organization in an email. “But the effect size remains relatively small and may be explained by residual or unmeasured confounding,” he cautioned.
“Ultimately, there do not seem to be enough data to support a change in clinical practice from this study alone, and, as a result, clinicians should continue to inform patients of the best available evidence regarding the benefits and risks of PPIs,” said Dr. Leiman, assistant professor of medicine, Division of Gastroenterology, Duke University Medical Center, Durham, N.C.
“Recent best practice advice from the American Gastroenterological Association does not recommend screening for insulin resistance among PPI users [and recommends that the decision to discontinue PPIs] should be based solely on the lack of an indication for PPI use, and not because of concern for PPI-associated adverse events,” he noted.
“Clinicians should be prepared to discuss the described risks associated with PPIs,” said Dr. Leiman, but they should “also feel comfortable affirming their safety profile and substantial efficacy in managing symptoms and preventing complications when prescribed for the appropriate indication.”
First-choice therapy for acid-related disorders
PPIs have become first-choice therapy for patients with acid-related disorders such as gastroesophageal reflux disease, Barrett esophagus, and peptic ulcer, and to prevent gastrointestinal bleeding while on nonsteroidal anti-inflammatory drugs (NSAIDs), Dr. Ciardullo and colleagues explain.
However, several studies have identified potential fractures, hypomagnesemia, gastric carcinoids, chronic kidney disease, dementia, and Clostridium difficile diarrhea with prolonged use of PPIs, and these agents can cause changes in the gut microbiome that may play a role in diabetes and other metabolic diseases.
To investigate a potential association between PPIs and type 2 diabetes, the researchers analyzed data from 777,420 patients age 40 and older who were newly treated with PPIs between 2010 and 2015 in Lombardy, Italy.
Of these, 50,540 patients were diagnosed with type 2 diabetes during follow-up until 2020 (a mean follow-up of 6.2 years and a diabetes incidence of 10.6 cases per 1,000 person-years).
The researchers matched 50,535 patients diagnosed with diabetes during follow-up with 50,535 control patients who had the same age, sex, and clinical status.
Patients were a mean age of 66 years and half were men. The most prescribed PPIs were pantoprazole and omeprazole, and the patients diagnosed with diabetes were more likely to use antihypertensives and lipid-lowering drugs.
Compared with patients who received PPIs for less than 8 weeks, those who received PPIs for 8 weeks to 6 months had a 19% increased risk of being diagnosed with diabetes during follow-up (odds ratio, 1.19; 95% confidence interval, 1.15-1.24), after adjusting for age, clinical profile, comorbidities, medical therapy, and PPI type.
Patients who received PPIs for 6 months to 2 years had a 43% increased risk of the outcome (OR, 1.43; 95% CI, 1.38-1.49), and those who received PPIs for more than 2 years had a 56% increased risk of the outcome (OR, 1.56; 95% CI, 1.49-1.64).
The researchers acknowledge limitations including that the study was not a randomized controlled trial, and it lacked information about over-the-counter medications and unmeasured confounders such as body mass index or family history of diabetes that may have affected the outcomes.
Dr. Leiman added that patients may have had prediabetes or undiagnosed diabetes and symptoms such as heartburn or dyspepsia arising from complications of insulin resistance, for which PPIs might have been prescribed.
The study was funded by a grant from the Italian Ministry of Education, University and Research. Dr. Ciardullo and Dr. Leiman have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Steroids show less effectiveness in older-onset UC
Intravenous steroids were less effective in ulcerative colitis patients with older-onset disease, compared with younger-onset patients, according to data from nearly 500 individuals.
A combination of rising ulcerative colitis rates and an aging population has driven an increase in older-onset UC worldwide, Shinji Okabayashi, MD, of Kyoto University, and colleagues wrote in a study published in Alimentary Pharmacology & Therapeutics.
Data on differences in disease history between younger- and older-onset cases have been inconsistent, but one meta-analysis suggested a higher rate of surgery in older-onset cases, the authors of the current study wrote. “The higher risk of surgery may be due to the difference in effectiveness of intravenous steroid treatment, which is one of the important treatment options to avoid surgery for a severe course of UC,” but data on the effectiveness of IV steroids for older-onset UC are lacking.
The researchers reviewed data from 467 adults with ulcerative colitis at 27 centers in Japan. The participants were hospitalized and received their initial intravenous steroids between April 2014 and July 2019. The treatment was a daily dose of 40 mg or more of IV prednisolone or its equivalent, with dosing according to current guidelines. The primary outcome was clinical remission after 30 days.
The study population included 83 patients with older-onset UC and 384 with younger-onset UC. No cutoff currently exists to classify UC by age; the researchers defined younger onset as patients diagnosed at younger than 60 years and older onset as those diagnosed at age 60 years and older. The median age of onset was 32 years in the younger-onset patients and 68 in the older-onset group.
Overall, 51.8% of older-onset patients and 65.6% of younger-onset patients had clinical remission at 30 days (adjusted risk ratio, 0.74; P = .009). The incidence of colectomy at 30 days was significantly higher in older-onset patients, compared with younger-onset patients (15.7% vs. 1.8%; P < .001).
The researchers also assessed risk of surgery and adverse events at 90 days as secondary outcomes. The risk of surgery was significantly higher in older-onset patients compared with younger-onset patients (20.5% vs. 3.1%; ARR, 8.92) as was the risk of adverse events (25.3% vs. 9.1%, ARR, 2.19). A total of four deaths occurred during the study period, all in older-onset patients.
In addition, the researchers found that clinical remission rates at 30 days in older patients with younger-onset UC was similar to that of younger patients with younger-onset UC.
Potential contributors to the lower effectiveness of intravenous steroids in older-onset UC include genetic susceptibility, gut microbiota, and environmental factors, the researchers noted. The dysregulated immune response in older-onset UC also might play a role in limiting the effectiveness of intravenous steroids in these patients.
The study findings were limited by several factors including the lack of data on genetic susceptibility, environmental factors, and gut microbiota, as well as the inclusion only of patients with moderate to severe disease, which might have contributed to the higher risk of surgery in older patients, the researchers said. Other potential limitations include the potential confounders of concomitant drugs and nutritional status, and the use of symptom-based scoring to determine clinical remission.
However, the overall results reflect data from a recent meta-analysis, and the current study “clearly suggests that one of the reasons for the poor prognosis in patients with older-onset UC is the lower effectiveness of intravenous steroid treatment, which is one of the important treatment options for a severe course of UC,” the researchers wrote.
“Further research is warranted to establish the optimal treatment strategies for moderate to severe older-onset UC,” they concluded.
Findings have value for high-risk patients
The study is of interest to clinicians in practice, Hamed Khalili, MD, of Massachusetts General Hospital, Boston, said in an interview. “The findings are largely consistent with prior studies that have shown older-onset IBD patients have higher risk of surgery,” said Dr. Khalili, who was not involved with the study.
“This study focuses on a smaller subset of patients with IBD who present with acute severe UC,” Dr. Khalili noted. “Since this is a higher-risk patient population, the findings that older-onset UC is associated with lower response to intravenous steroids could have direct clinical implications.”
The study was supported by the Japanese Society for Inflammatory Bowel Disease. The researchers had no relevant financial conflicts to disclose. Dr. Khalili had no financial conflicts to disclose.
Intravenous steroids were less effective in ulcerative colitis patients with older-onset disease, compared with younger-onset patients, according to data from nearly 500 individuals.
A combination of rising ulcerative colitis rates and an aging population has driven an increase in older-onset UC worldwide, Shinji Okabayashi, MD, of Kyoto University, and colleagues wrote in a study published in Alimentary Pharmacology & Therapeutics.
Data on differences in disease history between younger- and older-onset cases have been inconsistent, but one meta-analysis suggested a higher rate of surgery in older-onset cases, the authors of the current study wrote. “The higher risk of surgery may be due to the difference in effectiveness of intravenous steroid treatment, which is one of the important treatment options to avoid surgery for a severe course of UC,” but data on the effectiveness of IV steroids for older-onset UC are lacking.
The researchers reviewed data from 467 adults with ulcerative colitis at 27 centers in Japan. The participants were hospitalized and received their initial intravenous steroids between April 2014 and July 2019. The treatment was a daily dose of 40 mg or more of IV prednisolone or its equivalent, with dosing according to current guidelines. The primary outcome was clinical remission after 30 days.
The study population included 83 patients with older-onset UC and 384 with younger-onset UC. No cutoff currently exists to classify UC by age; the researchers defined younger onset as patients diagnosed at younger than 60 years and older onset as those diagnosed at age 60 years and older. The median age of onset was 32 years in the younger-onset patients and 68 in the older-onset group.
Overall, 51.8% of older-onset patients and 65.6% of younger-onset patients had clinical remission at 30 days (adjusted risk ratio, 0.74; P = .009). The incidence of colectomy at 30 days was significantly higher in older-onset patients, compared with younger-onset patients (15.7% vs. 1.8%; P < .001).
The researchers also assessed risk of surgery and adverse events at 90 days as secondary outcomes. The risk of surgery was significantly higher in older-onset patients compared with younger-onset patients (20.5% vs. 3.1%; ARR, 8.92) as was the risk of adverse events (25.3% vs. 9.1%, ARR, 2.19). A total of four deaths occurred during the study period, all in older-onset patients.
In addition, the researchers found that clinical remission rates at 30 days in older patients with younger-onset UC was similar to that of younger patients with younger-onset UC.
Potential contributors to the lower effectiveness of intravenous steroids in older-onset UC include genetic susceptibility, gut microbiota, and environmental factors, the researchers noted. The dysregulated immune response in older-onset UC also might play a role in limiting the effectiveness of intravenous steroids in these patients.
The study findings were limited by several factors including the lack of data on genetic susceptibility, environmental factors, and gut microbiota, as well as the inclusion only of patients with moderate to severe disease, which might have contributed to the higher risk of surgery in older patients, the researchers said. Other potential limitations include the potential confounders of concomitant drugs and nutritional status, and the use of symptom-based scoring to determine clinical remission.
However, the overall results reflect data from a recent meta-analysis, and the current study “clearly suggests that one of the reasons for the poor prognosis in patients with older-onset UC is the lower effectiveness of intravenous steroid treatment, which is one of the important treatment options for a severe course of UC,” the researchers wrote.
“Further research is warranted to establish the optimal treatment strategies for moderate to severe older-onset UC,” they concluded.
Findings have value for high-risk patients
The study is of interest to clinicians in practice, Hamed Khalili, MD, of Massachusetts General Hospital, Boston, said in an interview. “The findings are largely consistent with prior studies that have shown older-onset IBD patients have higher risk of surgery,” said Dr. Khalili, who was not involved with the study.
“This study focuses on a smaller subset of patients with IBD who present with acute severe UC,” Dr. Khalili noted. “Since this is a higher-risk patient population, the findings that older-onset UC is associated with lower response to intravenous steroids could have direct clinical implications.”
The study was supported by the Japanese Society for Inflammatory Bowel Disease. The researchers had no relevant financial conflicts to disclose. Dr. Khalili had no financial conflicts to disclose.
Intravenous steroids were less effective in ulcerative colitis patients with older-onset disease, compared with younger-onset patients, according to data from nearly 500 individuals.
A combination of rising ulcerative colitis rates and an aging population has driven an increase in older-onset UC worldwide, Shinji Okabayashi, MD, of Kyoto University, and colleagues wrote in a study published in Alimentary Pharmacology & Therapeutics.
Data on differences in disease history between younger- and older-onset cases have been inconsistent, but one meta-analysis suggested a higher rate of surgery in older-onset cases, the authors of the current study wrote. “The higher risk of surgery may be due to the difference in effectiveness of intravenous steroid treatment, which is one of the important treatment options to avoid surgery for a severe course of UC,” but data on the effectiveness of IV steroids for older-onset UC are lacking.
The researchers reviewed data from 467 adults with ulcerative colitis at 27 centers in Japan. The participants were hospitalized and received their initial intravenous steroids between April 2014 and July 2019. The treatment was a daily dose of 40 mg or more of IV prednisolone or its equivalent, with dosing according to current guidelines. The primary outcome was clinical remission after 30 days.
The study population included 83 patients with older-onset UC and 384 with younger-onset UC. No cutoff currently exists to classify UC by age; the researchers defined younger onset as patients diagnosed at younger than 60 years and older onset as those diagnosed at age 60 years and older. The median age of onset was 32 years in the younger-onset patients and 68 in the older-onset group.
Overall, 51.8% of older-onset patients and 65.6% of younger-onset patients had clinical remission at 30 days (adjusted risk ratio, 0.74; P = .009). The incidence of colectomy at 30 days was significantly higher in older-onset patients, compared with younger-onset patients (15.7% vs. 1.8%; P < .001).
The researchers also assessed risk of surgery and adverse events at 90 days as secondary outcomes. The risk of surgery was significantly higher in older-onset patients compared with younger-onset patients (20.5% vs. 3.1%; ARR, 8.92) as was the risk of adverse events (25.3% vs. 9.1%, ARR, 2.19). A total of four deaths occurred during the study period, all in older-onset patients.
In addition, the researchers found that clinical remission rates at 30 days in older patients with younger-onset UC was similar to that of younger patients with younger-onset UC.
Potential contributors to the lower effectiveness of intravenous steroids in older-onset UC include genetic susceptibility, gut microbiota, and environmental factors, the researchers noted. The dysregulated immune response in older-onset UC also might play a role in limiting the effectiveness of intravenous steroids in these patients.
The study findings were limited by several factors including the lack of data on genetic susceptibility, environmental factors, and gut microbiota, as well as the inclusion only of patients with moderate to severe disease, which might have contributed to the higher risk of surgery in older patients, the researchers said. Other potential limitations include the potential confounders of concomitant drugs and nutritional status, and the use of symptom-based scoring to determine clinical remission.
However, the overall results reflect data from a recent meta-analysis, and the current study “clearly suggests that one of the reasons for the poor prognosis in patients with older-onset UC is the lower effectiveness of intravenous steroid treatment, which is one of the important treatment options for a severe course of UC,” the researchers wrote.
“Further research is warranted to establish the optimal treatment strategies for moderate to severe older-onset UC,” they concluded.
Findings have value for high-risk patients
The study is of interest to clinicians in practice, Hamed Khalili, MD, of Massachusetts General Hospital, Boston, said in an interview. “The findings are largely consistent with prior studies that have shown older-onset IBD patients have higher risk of surgery,” said Dr. Khalili, who was not involved with the study.
“This study focuses on a smaller subset of patients with IBD who present with acute severe UC,” Dr. Khalili noted. “Since this is a higher-risk patient population, the findings that older-onset UC is associated with lower response to intravenous steroids could have direct clinical implications.”
The study was supported by the Japanese Society for Inflammatory Bowel Disease. The researchers had no relevant financial conflicts to disclose. Dr. Khalili had no financial conflicts to disclose.
FROM ALIMENTARY PHARMACOLOGY & THERAPEUTICS
Field Cancerization in Dermatology: Updates on Treatment Considerations and Emerging Therapies
There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.1 The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.
Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al4 updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.
Field-Directed Therapies
Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.5 The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.8 The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.9
Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).10 A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.11 Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.12
Field-directed treatment with erbium:YAG and CO2 lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.13 There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).14
Lesion-Directed Therapies
Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.15 Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.16
Oral Therapies
Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I2=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.19
Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.20 Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.21 The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.22
Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.23 Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.24 Still, the evidence supporting capecitabine does not include any controlled studies.
Novel Therapies
In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.25 Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.
Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.26 A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.27 However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.28 There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).
Final Thoughts
It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.
- Braakhuis BJM, Tabor MP, Kummer JA, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727-1730.
- Ashford BG, Clark J, Gupta R, et al. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: a search for prognostic markers and therapeutic targets. Head Neck. 2017;39:1462-1469. doi:10.1002/hed.24765
- Albibas AA, Rose-Zerilli MJJ, Lai C, et al. Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin. J Invest Dermatol. 2018;138:189-198. doi:10.1016/j.jid.2017.07.844
- Willenbrink TJ, Ruiz ES, Cornejo CM, et al. Field cancerization: definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol. 2020;83:709-717. doi:10.1016/j.jaad.2020.03.126
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi:10.1056/NEJMoa1811850
- Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116. doi:10.1172/JCI89820
- Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4:125476. doi:10.1172/jci.insight.125476
- Peuvrel L, Saint-Jean M, Quereux G, et al. 5-fluorouracil chemowraps for the treatment of multiple actinic keratoses. Eur J Dermatol. 2017;27:635-640. doi:10.1684/ejd.2017.3128
- Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85:E209-E233. doi:10.1016/j.jaad.2021.02.082
- Vegter S, Tolley K. A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe. PLoS One. 2014;9:E96829. doi:10.1371/journal.pone.0096829
- Zhu L, Wang P, Zhang G, et al. Conventional versus daylight photodynamic therapy for actinic keratosis: a randomized and prospective study in China. Photodiagnosis Photodyn Ther. 2018;24:366-371. doi:10.1016/j.pdpdt.2018.10.010
- Borgia F, Riso G, Catalano F, et al. Topical tacalcitol as neoadjuvant for photodynamic therapy of acral actinic keratoses: an intra-patient randomized study. Photodiagnosis Photodyn Ther. 2020;31:101803. doi:10.1016/j.pdpdt.2020.101803
- Tai F, Shah M, Pon K, et al. Laser resurfacing monotherapy for the treatment of actinic keratosis. J Cutan Med Surg. 2021;25:634-642. doi:10.1177/12034754211027515
- Steeb T, Schlager JG, Kohl C, et al. Laser-assisted photodynamic therapy for actinic keratosis: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:947-956. doi:10.1016/j.jaad.2018.09.021
- Intralesional chemotherapy for nonmelanoma skin cancer: a practical review. J Am Acad Dermatol. 2010;63:689-702. doi:10.1016/j.jaad.2009.09.048
- Maxfield L, Shah M, Schwartz C, et al. Intralesional 5-fluorouracil for the treatment of squamous cell carcinomas. J Am Acad Dermatol. 2021;84:1696-1697. doi:10.1016/j.jaad.2020.12.049
- Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-1626. doi:10.1056/NEJMoa1506197
- Surjana D, Halliday GM, Martin AJ, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497-1500. doi:10.1038/jid.2011.459
- Mainville L, Smilga AS, Fortin PR. Effect of nicotinamide in skin cancer and actinic keratoses chemoprophylaxis, and adverse effects related to nicotinamide: a systematic review and meta-analysis [published online February 8, 2022]. J Cutan Med Surg. doi:10.1177/12034754221078201
- Massey PR, Schmults CD, Li SJ, et al. Consensus-based recommendations on the prevention of squamous cell carcinoma in solid organ transplant recipients: a Delphi Consensus Statement. JAMA Dermatol. 2021;157:1219-1226. doi:10.1001/jamadermatol.2021.3180
- Tee LY, Sultana R, Tam SYC, et al. Chemoprevention of keratinocyte carcinoma and actinic keratosis in solid-organ transplant recipients: systematic review and meta-analyses. J Am Acad Dermatol. 2021;84:528-530. doi:10.1016/j.jaad.2020.04.160
- George R, Weightman W, Russ GR, et al. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol. 2002;43:269-273. doi:10.1046/j.1440-0960.2002.00613.x
- Schauder DM, Kim J, Nijhawan RI. Evaluation of the use of capecitabine for the treatment and prevention of actinic keratoses, squamous cell carcinoma, and basal cell carcinoma: a systematic review. JAMA Dermatol. 2020;156:1117-1124. doi:10.1001/jamadermatol.2020.2327
- Antoniolli LP, Escobar GF, Peruzzo J. Inflammatory actinic keratosis following capecitabine therapy. Dermatol Ther. 2020;33:E14082. doi:10.1111/dth.14082
- Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384:512-520. doi:10.1056/NEJMoa2024040
- Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16:4005-4015. doi:10.1158/1078-0432.CCR-10-0196
- Harrington KJ, Kong A, Mach N, et al. Talimogene laherparepvec and pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (MASTERKEY-232): a multicenter, phase 1b study. Clin Cancer Res. 2020;26:5153-5161. doi:10.1158/1078-0432.CCR-20-1170
- Nguyen TA, Offner M, Hamid O, et al. Complete and sustained remission of metastatic cutaneous squamous cell carcinoma in a liver transplant patient treated with talimogene laherparepvec. Dermatol Surg. 2021;47:820-822. doi:10.1097/DSS.0000000000002739
There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.1 The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.
Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al4 updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.
Field-Directed Therapies
Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.5 The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.8 The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.9
Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).10 A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.11 Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.12
Field-directed treatment with erbium:YAG and CO2 lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.13 There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).14
Lesion-Directed Therapies
Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.15 Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.16
Oral Therapies
Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I2=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.19
Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.20 Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.21 The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.22
Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.23 Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.24 Still, the evidence supporting capecitabine does not include any controlled studies.
Novel Therapies
In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.25 Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.
Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.26 A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.27 However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.28 There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).
Final Thoughts
It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.
There has been increasing awareness of field cancerization in dermatology and how it relates to actinic damage, actinic keratoses (AKs), and the development of cutaneous squamous cell carcinomas (SCCs). The concept of field cancerization, which was first described in the context of oropharyngeal SCCs, attempted to explain the repeated observation of local recurrences that were instead multiple primary oropharyngeal SCCs occurring within a specific region of tissue. It was hypothesized that the tissue surrounding a malignancy also harbors irreversible oncogenic damage and therefore predisposes the surrounding tissue to developing further malignancy.1 The development of additional malignant lesions would be considered distinct from a true recurrence of the original malignancy.
Field cancerization may be partially explained by a genetic basis, as mutations in the tumor suppressor gene, TP53—the most frequently observed mutation in cutaneous SCCs—also is found in sun-exposed but clinically normal skin.2,3 The finding of oncogenic mutations in nonlesional skin supports the theory of field cancerization, in which a region contains multiple genetically altered populations, some of which may progress to cancer. Because there currently is no widely accepted clinical definition or validated clinical measurement of field cancerization in dermatology, it may be difficult for dermatologists to recognize which patients may be at risk for developing further malignancy in a potential area of field cancerization. Willenbrink et al4 updated the definition of field cancerization in dermatology as “multifocal clinical atypia characterized by AKs or SCCs in situ with or without invasive disease occurring in a field exposed to chronic UV radiation.” Managing patients with field cancerization can be challenging. Herein, we discuss updates to nonsurgical field-directed and lesion-directed therapies as well as other emerging therapies.
Field-Directed Therapies
Topical 5-fluorouracil (5-FU) and imiquimod cream 5% used as field-directed therapies help reduce the extent of AKs and actinic damage in areas of possible field cancerization.5 The addition of calcipotriol to topical 5-FU, which theoretically augments the skin’s T-cell antitumor response via the cytokine thymic stromal lymphopoietin, recently has been studied using short treatment courses resulting in an 87.8% reduction in AKs compared to a 26.3% reduction with topical 5-FU alone (when used twice daily for 4 days) and conferred a reduced risk of cutaneous SCCs 3 years after treatment (hazard ratio, 0.215 [95% CI, 0.048-0.972]; P=.032).6,7 Chemowraps using topical 5-FU may be considered in more difficult-to-treat areas of field cancerization with multiple AKs or keratinocyte carcinomas of the lower extremities.8 The routine use of chemowraps—weekly application of 5-FU covered with an occlusive dressing—may be limited by the inability to control the extent of epidermal damage and subsequent systemic absorption. Ingenol mebutate, which was approved for treatment of AKs in 2012, was removed from both the European and US markets in 2020 because the medication may paradoxically increase the long-term incidence of skin cancer.9
Meta-analysis has shown that photodynamic therapy (PDT) with aminolevulinic acid demonstrated complete AK clearance in 75.8% of patients (N=156)(95% CI, 55.4%-96.2%).10 A more recent method of PDT using natural sunlight as the activation source demonstrated AK clearance of 95.5%, and it appeared to be a less painful alternative to traditional PDT.11 Tacalcitol, another form of vitamin D, also has been shown to enhance the efficacy of PDT for AKs.12
Field-directed treatment with erbium:YAG and CO2 lasers, which physically remove the actinically damaged epidermis, have been shown to possibly be as efficacious as topical 5-FU and 30% trichloroacetic acid (TCA) but possibly inferior to PDT.13 There has been growing interest in laser-assisted therapy, in which an ablative fractional laser is used to generate microscopic channels to theoretically enhance the absorption of a topical medication. A meta-analysis of the use of laser-assisted therapy for photosensitizing agents in PDT demonstrated a 33% increased chance of AK clearance compared to PDT alone (P<.01).14
Lesion-Directed Therapies
Multiple KAs or cutaneous SCCs may develop in an area of field cancerization, and surgically treating these multiple lesions in a concentrated area may be challenging. Intralesional agents, including methotrexate, 5-FU, bleomycin, and interferon, are known treatments for KAs.15 Intralesional 5-FU (25 mg once weekly for 3–4 weeks) in particular produced complete resolution in 92% of cutaneous SCCs and may be optimal for multiple or rapidly growing lesions, especially on the extremities.16
Oral Therapies
Oral therapies are considered in high-risk patients with multiple or recurrent cutaneous SCCs or in those who are immunosuppressed. Two trials demonstrated that nicotinamide 500 mg twice daily for 4 and 12 months decreased AKs by 29% to 35% and 13% (average of 3–5 fewer AKs as compared to baseline), respectively.17,18 A meta-analysis found a reduction of cutaneous SCCs (rate ratio, 0.48 [95% CI, 0.26-0.88]; I2=67%; 552 patients, 5 trials), and given the favorable safety profile, nicotinamide can be considered for chemoprevention.19
Acitretin, shown to reduce AKs by 13.4% to 50%, is the primary oral chemoprevention recommended in transplant recipients.20 Interestingly, a recent meta-analysis failed to find significant differences between the efficacy of acitretin and nicotinamide.21 The tolerability of acitretin requires serious consideration, as 52.2% of patients withdrew due to adverse effects in one trial.22
Capecitabine (250–1150 mg twice daily), the oral form of 5-FU, decreased the incidence of AKs and cutaneous SCCs in 53% and 72% of transplant recipients, respectively.23 Although several reports observed paradoxical eruptions of AKs following capecitabine for other malignancies, this actually underscores the efficacy of capecitabine, as the newly emerged AKs resolved thereafter.24 Still, the evidence supporting capecitabine does not include any controlled studies.
Novel Therapies
In 2021, tirbanibulin ointment 1%, a Src tyrosine kinase inhibitor of tubulin polymerization that induces p53 expression and subsequent cell death, was approved by the US Food and Drug Administration for the treatment of AKs.25 Two trials reported AK clearance rates of 44% and 54% with application of tirbanibulin once daily for 5 days (vs 5% and 13%, respectively, with placebo, each with P<.001) at 2 months and a sustained clearance rate of 27% at 1 year. The predominant adverse effects were local skin reactions, including application-site pain, pruritus, mild erythema, or scaling. Unlike in other treatments such as 5-FU or cryotherapy, erosions, dyspigmentation, or scarring were not notably observed.
Intralesional talimogene laherparepvec (T-VEC), an oncolytic, genetically modified herpes simplex virus type 1 that incites antitumor immune responses, received US Food and Drug Administration approval in 2015 for the treatment of cutaneous and lymph node metastases of melanoma that are unable to be surgically resected. More recently, T-VEC has been investigated for oropharyngeal SCC. A phase 1 and phase 2 trial of 17 stage III/IV SCC patients receiving T-VEC and cisplatin demonstrated pathologic remission in 14 of 15 (93%) patients, with 82.4% survival at 29 months.26 A multicenter phase 1b trial of 36 patients with recurrent or metastatic head and neck SCCs treated with T-VEC and pembrolizumab exhibited a tolerable safety profile, and 5 cases had a partial response.27 However, phase 3 trials of T-VEC have yet to be pursued. Regarding its potential use for cutaneous SCCs, it has been reportedly used in a liver transplant recipient with metastatic cutaneous SCCs who received 2 doses of T-VEC (1 month apart) and attained remission of disease.28 There currently is a phase 2 trial examining the effectiveness of T-VEC in patients with cutaneous SCCs (ClinicalTrials.gov identifier NCT03714828).
Final Thoughts
It is important for dermatologists to bear in mind the possible role of field cancerization in their comprehensive care of patients at risk for multiple skin cancers. Management of areas of field cancerization can be challenging, particularly in patients who develop multiple KAs or cutaneous SCCs in a concentrated area and may need to involve different levels of treatment options, including field-directed therapies and lesion-directed therapies, as well as systemic chemoprevention.
- Braakhuis BJM, Tabor MP, Kummer JA, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727-1730.
- Ashford BG, Clark J, Gupta R, et al. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: a search for prognostic markers and therapeutic targets. Head Neck. 2017;39:1462-1469. doi:10.1002/hed.24765
- Albibas AA, Rose-Zerilli MJJ, Lai C, et al. Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin. J Invest Dermatol. 2018;138:189-198. doi:10.1016/j.jid.2017.07.844
- Willenbrink TJ, Ruiz ES, Cornejo CM, et al. Field cancerization: definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol. 2020;83:709-717. doi:10.1016/j.jaad.2020.03.126
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi:10.1056/NEJMoa1811850
- Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116. doi:10.1172/JCI89820
- Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4:125476. doi:10.1172/jci.insight.125476
- Peuvrel L, Saint-Jean M, Quereux G, et al. 5-fluorouracil chemowraps for the treatment of multiple actinic keratoses. Eur J Dermatol. 2017;27:635-640. doi:10.1684/ejd.2017.3128
- Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85:E209-E233. doi:10.1016/j.jaad.2021.02.082
- Vegter S, Tolley K. A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe. PLoS One. 2014;9:E96829. doi:10.1371/journal.pone.0096829
- Zhu L, Wang P, Zhang G, et al. Conventional versus daylight photodynamic therapy for actinic keratosis: a randomized and prospective study in China. Photodiagnosis Photodyn Ther. 2018;24:366-371. doi:10.1016/j.pdpdt.2018.10.010
- Borgia F, Riso G, Catalano F, et al. Topical tacalcitol as neoadjuvant for photodynamic therapy of acral actinic keratoses: an intra-patient randomized study. Photodiagnosis Photodyn Ther. 2020;31:101803. doi:10.1016/j.pdpdt.2020.101803
- Tai F, Shah M, Pon K, et al. Laser resurfacing monotherapy for the treatment of actinic keratosis. J Cutan Med Surg. 2021;25:634-642. doi:10.1177/12034754211027515
- Steeb T, Schlager JG, Kohl C, et al. Laser-assisted photodynamic therapy for actinic keratosis: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:947-956. doi:10.1016/j.jaad.2018.09.021
- Intralesional chemotherapy for nonmelanoma skin cancer: a practical review. J Am Acad Dermatol. 2010;63:689-702. doi:10.1016/j.jaad.2009.09.048
- Maxfield L, Shah M, Schwartz C, et al. Intralesional 5-fluorouracil for the treatment of squamous cell carcinomas. J Am Acad Dermatol. 2021;84:1696-1697. doi:10.1016/j.jaad.2020.12.049
- Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-1626. doi:10.1056/NEJMoa1506197
- Surjana D, Halliday GM, Martin AJ, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497-1500. doi:10.1038/jid.2011.459
- Mainville L, Smilga AS, Fortin PR. Effect of nicotinamide in skin cancer and actinic keratoses chemoprophylaxis, and adverse effects related to nicotinamide: a systematic review and meta-analysis [published online February 8, 2022]. J Cutan Med Surg. doi:10.1177/12034754221078201
- Massey PR, Schmults CD, Li SJ, et al. Consensus-based recommendations on the prevention of squamous cell carcinoma in solid organ transplant recipients: a Delphi Consensus Statement. JAMA Dermatol. 2021;157:1219-1226. doi:10.1001/jamadermatol.2021.3180
- Tee LY, Sultana R, Tam SYC, et al. Chemoprevention of keratinocyte carcinoma and actinic keratosis in solid-organ transplant recipients: systematic review and meta-analyses. J Am Acad Dermatol. 2021;84:528-530. doi:10.1016/j.jaad.2020.04.160
- George R, Weightman W, Russ GR, et al. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol. 2002;43:269-273. doi:10.1046/j.1440-0960.2002.00613.x
- Schauder DM, Kim J, Nijhawan RI. Evaluation of the use of capecitabine for the treatment and prevention of actinic keratoses, squamous cell carcinoma, and basal cell carcinoma: a systematic review. JAMA Dermatol. 2020;156:1117-1124. doi:10.1001/jamadermatol.2020.2327
- Antoniolli LP, Escobar GF, Peruzzo J. Inflammatory actinic keratosis following capecitabine therapy. Dermatol Ther. 2020;33:E14082. doi:10.1111/dth.14082
- Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384:512-520. doi:10.1056/NEJMoa2024040
- Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16:4005-4015. doi:10.1158/1078-0432.CCR-10-0196
- Harrington KJ, Kong A, Mach N, et al. Talimogene laherparepvec and pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (MASTERKEY-232): a multicenter, phase 1b study. Clin Cancer Res. 2020;26:5153-5161. doi:10.1158/1078-0432.CCR-20-1170
- Nguyen TA, Offner M, Hamid O, et al. Complete and sustained remission of metastatic cutaneous squamous cell carcinoma in a liver transplant patient treated with talimogene laherparepvec. Dermatol Surg. 2021;47:820-822. doi:10.1097/DSS.0000000000002739
- Braakhuis BJM, Tabor MP, Kummer JA, et al. A genetic explanation of Slaughter’s concept of field cancerization: evidence and clinical implications. Cancer Res. 2003;63:1727-1730.
- Ashford BG, Clark J, Gupta R, et al. Reviewing the genetic alterations in high-risk cutaneous squamous cell carcinoma: a search for prognostic markers and therapeutic targets. Head Neck. 2017;39:1462-1469. doi:10.1002/hed.24765
- Albibas AA, Rose-Zerilli MJJ, Lai C, et al. Subclonal evolution of cancer-related gene mutations in p53 immunopositive patches in human skin. J Invest Dermatol. 2018;138:189-198. doi:10.1016/j.jid.2017.07.844
- Willenbrink TJ, Ruiz ES, Cornejo CM, et al. Field cancerization: definition, epidemiology, risk factors, and outcomes. J Am Acad Dermatol. 2020;83:709-717. doi:10.1016/j.jaad.2020.03.126
- Jansen MHE, Kessels JPHM, Nelemans PJ, et al. Randomized trial of four treatment approaches for actinic keratosis. N Engl J Med. 2019;380:935-946. doi:10.1056/NEJMoa1811850
- Cunningham TJ, Tabacchi M, Eliane JP, et al. Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy. J Clin Invest. 2017;127:106-116. doi:10.1172/JCI89820
- Rosenberg AR, Tabacchi M, Ngo KH, et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight. 2019;4:125476. doi:10.1172/jci.insight.125476
- Peuvrel L, Saint-Jean M, Quereux G, et al. 5-fluorouracil chemowraps for the treatment of multiple actinic keratoses. Eur J Dermatol. 2017;27:635-640. doi:10.1684/ejd.2017.3128
- Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. J Am Acad Dermatol. 2021;85:E209-E233. doi:10.1016/j.jaad.2021.02.082
- Vegter S, Tolley K. A network meta-analysis of the relative efficacy of treatments for actinic keratosis of the face or scalp in Europe. PLoS One. 2014;9:E96829. doi:10.1371/journal.pone.0096829
- Zhu L, Wang P, Zhang G, et al. Conventional versus daylight photodynamic therapy for actinic keratosis: a randomized and prospective study in China. Photodiagnosis Photodyn Ther. 2018;24:366-371. doi:10.1016/j.pdpdt.2018.10.010
- Borgia F, Riso G, Catalano F, et al. Topical tacalcitol as neoadjuvant for photodynamic therapy of acral actinic keratoses: an intra-patient randomized study. Photodiagnosis Photodyn Ther. 2020;31:101803. doi:10.1016/j.pdpdt.2020.101803
- Tai F, Shah M, Pon K, et al. Laser resurfacing monotherapy for the treatment of actinic keratosis. J Cutan Med Surg. 2021;25:634-642. doi:10.1177/12034754211027515
- Steeb T, Schlager JG, Kohl C, et al. Laser-assisted photodynamic therapy for actinic keratosis: a systematic review and meta-analysis. J Am Acad Dermatol. 2019;80:947-956. doi:10.1016/j.jaad.2018.09.021
- Intralesional chemotherapy for nonmelanoma skin cancer: a practical review. J Am Acad Dermatol. 2010;63:689-702. doi:10.1016/j.jaad.2009.09.048
- Maxfield L, Shah M, Schwartz C, et al. Intralesional 5-fluorouracil for the treatment of squamous cell carcinomas. J Am Acad Dermatol. 2021;84:1696-1697. doi:10.1016/j.jaad.2020.12.049
- Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373:1618-1626. doi:10.1056/NEJMoa1506197
- Surjana D, Halliday GM, Martin AJ, et al. Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials. J Invest Dermatol. 2012;132:1497-1500. doi:10.1038/jid.2011.459
- Mainville L, Smilga AS, Fortin PR. Effect of nicotinamide in skin cancer and actinic keratoses chemoprophylaxis, and adverse effects related to nicotinamide: a systematic review and meta-analysis [published online February 8, 2022]. J Cutan Med Surg. doi:10.1177/12034754221078201
- Massey PR, Schmults CD, Li SJ, et al. Consensus-based recommendations on the prevention of squamous cell carcinoma in solid organ transplant recipients: a Delphi Consensus Statement. JAMA Dermatol. 2021;157:1219-1226. doi:10.1001/jamadermatol.2021.3180
- Tee LY, Sultana R, Tam SYC, et al. Chemoprevention of keratinocyte carcinoma and actinic keratosis in solid-organ transplant recipients: systematic review and meta-analyses. J Am Acad Dermatol. 2021;84:528-530. doi:10.1016/j.jaad.2020.04.160
- George R, Weightman W, Russ GR, et al. Acitretin for chemoprevention of non-melanoma skin cancers in renal transplant recipients. Australas J Dermatol. 2002;43:269-273. doi:10.1046/j.1440-0960.2002.00613.x
- Schauder DM, Kim J, Nijhawan RI. Evaluation of the use of capecitabine for the treatment and prevention of actinic keratoses, squamous cell carcinoma, and basal cell carcinoma: a systematic review. JAMA Dermatol. 2020;156:1117-1124. doi:10.1001/jamadermatol.2020.2327
- Antoniolli LP, Escobar GF, Peruzzo J. Inflammatory actinic keratosis following capecitabine therapy. Dermatol Ther. 2020;33:E14082. doi:10.1111/dth.14082
- Blauvelt A, Kempers S, Lain E, et al. Phase 3 trials of tirbanibulin ointment for actinic keratosis. N Engl J Med. 2021;384:512-520. doi:10.1056/NEJMoa2024040
- Harrington KJ, Hingorani M, Tanay MA, et al. Phase I/II study of oncolytic HSV GM-CSF in combination with radiotherapy and cisplatin in untreated stage III/IV squamous cell cancer of the head and neck. Clin Cancer Res. 2010;16:4005-4015. doi:10.1158/1078-0432.CCR-10-0196
- Harrington KJ, Kong A, Mach N, et al. Talimogene laherparepvec and pembrolizumab in recurrent or metastatic squamous cell carcinoma of the head and neck (MASTERKEY-232): a multicenter, phase 1b study. Clin Cancer Res. 2020;26:5153-5161. doi:10.1158/1078-0432.CCR-20-1170
- Nguyen TA, Offner M, Hamid O, et al. Complete and sustained remission of metastatic cutaneous squamous cell carcinoma in a liver transplant patient treated with talimogene laherparepvec. Dermatol Surg. 2021;47:820-822. doi:10.1097/DSS.0000000000002739
Innocent doc sued after 'secret' medical expert says claim has merit
When the hospital’s trauma team could not get an IV inserted into an accident victim, they called Illinois emergency physician William Sullivan, DO, JD, for help. Dr. Sullivan, who is based in the Chicago suburb of Frankfort, inserted a central line into the patient’s leg on his first attempt – a task that took about 20 minutes.
A year later, Dr. Sullivan was shocked and angry to learn he was being sued by the trauma patient’s family. Inserting the line was his only interaction with the woman, and he had no role in her care management, he said. Yet, the suit claimed he was negligent for failing to diagnose the patient with internal bleeding and for not performing surgery.
“The lawsuit put a lot of stress on our family,” Dr. Sullivan recalled. “At the time my wife was pregnant. I was in law school, and I was also working full time in the ER to support our family. I remember my wife crying on the couch after reading the complaint and asking how the plaintiff’s attorney could get away with making the allegations he made.”
Dr. Sullivan soon learned that 15 medical providers in the patient’s medical record were named as defendants. This included the director of the radiology department, whose name was on a radiology report as “director” but who was actually out of the country when the incident occurred.
Despite some of the accusations being impossible, a medical expert had claimed there was a “meritorious claim” against every health professional named in the suit. Illinois is among the 28 states that require plaintiffs’ attorneys to file an affidavit of merit for medical malpractice claims to move forward.
Dr. Sullivan wondered who would endorse such outlandish accusations, but the expert’s identity was a mystery. According to Illinois law, About one-third of states with merit requirements permit anonymous experts, according to research and attorneys familiar with the issue.
Because the expert’s identity remains hidden, physicians have no way of knowing whether they were qualified to render an opinion, Dr. Sullivan said. The loopholes can drag out frivolous claims and waste significant time and expense, say legal experts. Frequently, it takes a year or more before innocent physicians are dismissed from unfounded lawsuits by the court or dropped when plaintiffs can’t support the claim.
“It’s hugely frustrating,” said Bruce Montoya, JD, a Colorado medical liability defense attorney. “You have an expert who is not disclosed. Further down the road, when experts are being deposed, the plaintiff does not have to reveal whether any of those testifying experts is the same one who certified the case. You never get to determine whether they, in fact, had a certificate reviewer who was legitimate.”
The laws have led to a recent outcry among physicians and fueled a revised resolution by the American College of Emergency Physicians (ACEP) denouncing anonymous affidavits of merit. (The revision has not yet been published online.)
“The minute experts are identified, they can be vetted,” said Rade B. Vukmir, MD, JD, chair of ACEP’s Medical Legal Committee. “There are reasons that you want to clarify the qualification and veracity of the witness. [Anonymous affidavits of merit] don’t allow that, and there’s something inherently wrong with that.”
Because the identities of consulting experts are unknown, it’s hard to know how many are unqualified. Expert witnesses who testify during trials, on the other hand, have long come under scrutiny for questionable qualifications. Some have come under fire for allegedly lying under oath about their experience, misrepresenting their credentials, and falsely representing their knowledge.
“Considering the known problem of potentially unethical expert witness testimony at trial, there’s is the potential likelihood that experts in anonymous affidavits of merit may sometimes lack the qualifications to give opinions,” said Dr. Vukmir, an emergency care physician in Pittsburgh.
Attorneys: Hidden experts increase costs, waste time
In Colorado, Mr. Montoya has seen firsthand how anonymous experts can prolong questionable claims and burden defendants.
Like Illinois, Colorado does not require attorneys to identify the medical experts used to fulfill its certificate of review statute. The expert consulted must have expertise in the same area of the alleged negligence, but does not have to practice in the same specialty, and the statute allows one expert to certify a lawsuit against multiple doctors.
In a recent case, Mr. Montoya represented a Denver neurosurgeon who was sued along with multiple other health care professionals. From the outset, Mr. Montoya argued the claim had no merit against the neurosurgeon, but the plaintiff’s attorney refused to dismiss the physician. Mr. Montoya asked whether the expert consulted for the certificate of merit was a neurosurgeon, but the attorney declined to disclose that information, he said.
The case progressed and Mr. Montoya eventually asked the judge to review the certificate of merit. By law, a judge can confidentially review the certificate of merit and decide whether it aligns with the state statute, but without disclosing the expert’s identity to the defense. The judge ruled the certificate appeared to conform with state law, and the case continued.
A year later, as both sides were getting ready to disclose their experts who would testify, Mr. Montoya again argued the neurosurgeon should be dropped from the suit. This time, he warned if the claim continued against the neurosurgeon, the defense would be filing a motion for summary judgment and pursuing attorney fees and costs. Colorado law allows for such fees if the filing or pursuit of an action is frivolous.
“Boom, my client was dismissed,” Mr. Montoya said. “This is a year later, after multiple conferences among the attorneys, multiple pleadings filed, expert witnesses retained to review the care, discovery exchanged, and records obtained. If we had [a stronger] certificate of review statute, it would have been a different ballgame. It’s never going to get a year down the road.”
In New York, physician defendants have experienced similar woes. The state’s law requires plaintiffs’ attorneys to certify that they consulted with a physician prior to filing the claim, and that they believe based on that discussion, there’s a reasonable basis for the claim to move forward. Attorneys are not required to disclose the expert’s identity.
The law also allows “an out,” explained Morris Auster, JD, senior vice president and chief legislative counsel for the Medical Society of the State of New York. If the attorney made three separate attempts to obtain a consultation, and all three experts would not agree to the consultation, the lawsuit can be filed anyway, he said.
“From our standpoint, it’s important to have an affidavit of merit requirement; it’s better than not having it,” Mr. Auster said. “But its effectiveness in providing control over the filing of lawsuits in New York has never been as strong as it could’ve been.”
Mr. Auster notes that New York has some of the highest liability costs in the country in addition to doctors paying some of the steepest medical liability insurance premiums.
“This really affects a lot of physicians and it’s driving physicians into employment arrangements, so they don’t have to deal with it on their own,” he said. “We support a number of measures to address these significantly high costs, and stronger certificate of merit requirements would certainly be one of those advocacy goals.”
Why are anonymous experts allowed?
Certificates of merit that shield the identity of consultants encourage a greater pool of physicians willing to review cases, said J. Matthew Dudley, JD, president of the Illinois Trial Lawyers Association. When the requirements first went into effect in Illinois, there was significant animosity among physicians toward doctors who testified in medical malpractice cases for patients, Mr. Dudley explained.
“Sometimes they would be ostracized from their professional societies, or it would hurt a referral relationship.” he said. “Over time, that animosity has lessened, but there was a concern that if the identity of physicians in certificates of merit weren’t protected, then doctors would not look at cases for patients.”
This would result in additional barriers for patients and their attorneys in pursuing their legal rights, Mr. Dudley said. He said Illinois’ certificate of merit statute is successful in fulfilling its intended purpose, and he has not seen any statistical evidence to suggest otherwise.
“It has proven effective at decreasing filings in medical malpractice and effectively screening medical malpractice cases,” he said. “Certificates of merit help to decrease filings by firms that aren’t that experienced in dealing with those kinds of cases.”
Kentucky is another state that does not require attorneys to identity the experts consulted for certificates of merit. Malpractice defense attorney Andrew DeSimone, JD, who practices in Kentucky, said this isn’t a problem since attorneys eventually must disclose the expert witnesses who will testify at trial.
“Knowing the name behind the certificate of merit is not that pertinent,” Mr. DeSimone said. “Physicians and their attorneys will ultimately have the chance to question and evaluate the expert witnesses used at trial. The certificate of merit is designed to weed out totally frivolous cases that do not have expert support. It’s not designed to be a trial on the merits.”
The belief that plaintiffs’ attorneys frequently bring weak cases and use unqualified experts to certify claims is not realistic or logical, added Sean Domnick, JD, a Florida medical malpractice attorney and vice president for the American Association for Justice. Medical malpractice cases are extremely challenging for plaintiffs – and they’re expensive, Mr. Domnick said.
“We can’t afford to take bad cases,” he said. “For me to take on a medical malpractice case, it’s not unusual for me to spend well over $100,000. Remember, if we lose, I don’t get that money back and I don’t get paid. Why in the world would a plaintiff take on that type of a burden for a case they didn’t believe in? The logic escapes me.”
In Florida, where Mr. Domnick practices, plaintiffs’ attorneys must send their certificates of merit to the defense with the expert identified. Domnick believes the requirement is a hindrance.
“It creates a delay that is unnecessary in a system that is already designed to wear our clients down,” he said. “It’s just another component that makes it harder on them.”
Hidden experts may insulate plaintiffs’ attorneys from liability
Dr. Sullivan, the Illinois emergency physician, was ultimately dismissed from the multiparty lawsuit, but not for roughly 18 months. After the dismissal, he fought back. He sued the plaintiff’s law firm for malicious prosecution, negligence in hiring, and relying on the opinion of an expert who was unqualified to render an opinion against an emergency physician.
The law firm, however, argued that it was immune from liability because it reasonably relied on the expert’s opinion as required by Illinois law. A trial court agreed with the plaintiffs’ firm. The judge denied Dr. Sullivan’s request to identify the expert, ruling there was no finding that the affidavit was untrue or made without reasonable cause. Dr. Sullivan appealed, and the appellate court upheld the trial’s court decision.
“As happened with my case, law firms can use the affidavit as a defense against countersuits or motions for sanctions,” Dr. Sullivan said. “Although the certificate of merit is intended to prevent attorneys from filing frivolous cases, it can also have the opposite effect of helping to insulate plaintiff attorneys from liability for filing a frivolous lawsuit.”
In Colorado, complaints about the state’s certificate of merit statute have gone before the Colorado Supreme Court. In one case, a lower court ruled that a certificate of merit was deficient because the consultants were not chiropractors. In another case, a nurse defendant argued the claim’s certificate of review was insufficient because the consulting expert was a physician.
In both instances, Colorado judges held the state’s statute does not require consultants to be in the same profession or the same specialty as the health professional defendant.
In New York, meanwhile, Mr. Auster said several bills to strengthen the state’s certificate of merit requirements have failed in recent years.
“It’s hard to say whether it will improve anytime soon,” he said. “The trial lawyers are a very powerful advocacy force in the state, and they tend to oppose even the slightest of changes in civil liability. [In addition], some of these issues have been put on a lower tier because of trying to manage the pandemic.”
Ultimately, Dr. Sullivan said that courts and legislatures need to strongly consider the ethics of allowing anonymous experts to provide testimony against defendant physicians.
“I also think we need to consider how the notion of a secret expert comports with a defendant physician’s due process,” he said. “If an expert’s opinion is appropriate, why would there be a need to shroud one’s identity in a veil of secrecy?”
A version of this article first appeared on Medscape.com.
When the hospital’s trauma team could not get an IV inserted into an accident victim, they called Illinois emergency physician William Sullivan, DO, JD, for help. Dr. Sullivan, who is based in the Chicago suburb of Frankfort, inserted a central line into the patient’s leg on his first attempt – a task that took about 20 minutes.
A year later, Dr. Sullivan was shocked and angry to learn he was being sued by the trauma patient’s family. Inserting the line was his only interaction with the woman, and he had no role in her care management, he said. Yet, the suit claimed he was negligent for failing to diagnose the patient with internal bleeding and for not performing surgery.
“The lawsuit put a lot of stress on our family,” Dr. Sullivan recalled. “At the time my wife was pregnant. I was in law school, and I was also working full time in the ER to support our family. I remember my wife crying on the couch after reading the complaint and asking how the plaintiff’s attorney could get away with making the allegations he made.”
Dr. Sullivan soon learned that 15 medical providers in the patient’s medical record were named as defendants. This included the director of the radiology department, whose name was on a radiology report as “director” but who was actually out of the country when the incident occurred.
Despite some of the accusations being impossible, a medical expert had claimed there was a “meritorious claim” against every health professional named in the suit. Illinois is among the 28 states that require plaintiffs’ attorneys to file an affidavit of merit for medical malpractice claims to move forward.
Dr. Sullivan wondered who would endorse such outlandish accusations, but the expert’s identity was a mystery. According to Illinois law, About one-third of states with merit requirements permit anonymous experts, according to research and attorneys familiar with the issue.
Because the expert’s identity remains hidden, physicians have no way of knowing whether they were qualified to render an opinion, Dr. Sullivan said. The loopholes can drag out frivolous claims and waste significant time and expense, say legal experts. Frequently, it takes a year or more before innocent physicians are dismissed from unfounded lawsuits by the court or dropped when plaintiffs can’t support the claim.
“It’s hugely frustrating,” said Bruce Montoya, JD, a Colorado medical liability defense attorney. “You have an expert who is not disclosed. Further down the road, when experts are being deposed, the plaintiff does not have to reveal whether any of those testifying experts is the same one who certified the case. You never get to determine whether they, in fact, had a certificate reviewer who was legitimate.”
The laws have led to a recent outcry among physicians and fueled a revised resolution by the American College of Emergency Physicians (ACEP) denouncing anonymous affidavits of merit. (The revision has not yet been published online.)
“The minute experts are identified, they can be vetted,” said Rade B. Vukmir, MD, JD, chair of ACEP’s Medical Legal Committee. “There are reasons that you want to clarify the qualification and veracity of the witness. [Anonymous affidavits of merit] don’t allow that, and there’s something inherently wrong with that.”
Because the identities of consulting experts are unknown, it’s hard to know how many are unqualified. Expert witnesses who testify during trials, on the other hand, have long come under scrutiny for questionable qualifications. Some have come under fire for allegedly lying under oath about their experience, misrepresenting their credentials, and falsely representing their knowledge.
“Considering the known problem of potentially unethical expert witness testimony at trial, there’s is the potential likelihood that experts in anonymous affidavits of merit may sometimes lack the qualifications to give opinions,” said Dr. Vukmir, an emergency care physician in Pittsburgh.
Attorneys: Hidden experts increase costs, waste time
In Colorado, Mr. Montoya has seen firsthand how anonymous experts can prolong questionable claims and burden defendants.
Like Illinois, Colorado does not require attorneys to identify the medical experts used to fulfill its certificate of review statute. The expert consulted must have expertise in the same area of the alleged negligence, but does not have to practice in the same specialty, and the statute allows one expert to certify a lawsuit against multiple doctors.
In a recent case, Mr. Montoya represented a Denver neurosurgeon who was sued along with multiple other health care professionals. From the outset, Mr. Montoya argued the claim had no merit against the neurosurgeon, but the plaintiff’s attorney refused to dismiss the physician. Mr. Montoya asked whether the expert consulted for the certificate of merit was a neurosurgeon, but the attorney declined to disclose that information, he said.
The case progressed and Mr. Montoya eventually asked the judge to review the certificate of merit. By law, a judge can confidentially review the certificate of merit and decide whether it aligns with the state statute, but without disclosing the expert’s identity to the defense. The judge ruled the certificate appeared to conform with state law, and the case continued.
A year later, as both sides were getting ready to disclose their experts who would testify, Mr. Montoya again argued the neurosurgeon should be dropped from the suit. This time, he warned if the claim continued against the neurosurgeon, the defense would be filing a motion for summary judgment and pursuing attorney fees and costs. Colorado law allows for such fees if the filing or pursuit of an action is frivolous.
“Boom, my client was dismissed,” Mr. Montoya said. “This is a year later, after multiple conferences among the attorneys, multiple pleadings filed, expert witnesses retained to review the care, discovery exchanged, and records obtained. If we had [a stronger] certificate of review statute, it would have been a different ballgame. It’s never going to get a year down the road.”
In New York, physician defendants have experienced similar woes. The state’s law requires plaintiffs’ attorneys to certify that they consulted with a physician prior to filing the claim, and that they believe based on that discussion, there’s a reasonable basis for the claim to move forward. Attorneys are not required to disclose the expert’s identity.
The law also allows “an out,” explained Morris Auster, JD, senior vice president and chief legislative counsel for the Medical Society of the State of New York. If the attorney made three separate attempts to obtain a consultation, and all three experts would not agree to the consultation, the lawsuit can be filed anyway, he said.
“From our standpoint, it’s important to have an affidavit of merit requirement; it’s better than not having it,” Mr. Auster said. “But its effectiveness in providing control over the filing of lawsuits in New York has never been as strong as it could’ve been.”
Mr. Auster notes that New York has some of the highest liability costs in the country in addition to doctors paying some of the steepest medical liability insurance premiums.
“This really affects a lot of physicians and it’s driving physicians into employment arrangements, so they don’t have to deal with it on their own,” he said. “We support a number of measures to address these significantly high costs, and stronger certificate of merit requirements would certainly be one of those advocacy goals.”
Why are anonymous experts allowed?
Certificates of merit that shield the identity of consultants encourage a greater pool of physicians willing to review cases, said J. Matthew Dudley, JD, president of the Illinois Trial Lawyers Association. When the requirements first went into effect in Illinois, there was significant animosity among physicians toward doctors who testified in medical malpractice cases for patients, Mr. Dudley explained.
“Sometimes they would be ostracized from their professional societies, or it would hurt a referral relationship.” he said. “Over time, that animosity has lessened, but there was a concern that if the identity of physicians in certificates of merit weren’t protected, then doctors would not look at cases for patients.”
This would result in additional barriers for patients and their attorneys in pursuing their legal rights, Mr. Dudley said. He said Illinois’ certificate of merit statute is successful in fulfilling its intended purpose, and he has not seen any statistical evidence to suggest otherwise.
“It has proven effective at decreasing filings in medical malpractice and effectively screening medical malpractice cases,” he said. “Certificates of merit help to decrease filings by firms that aren’t that experienced in dealing with those kinds of cases.”
Kentucky is another state that does not require attorneys to identity the experts consulted for certificates of merit. Malpractice defense attorney Andrew DeSimone, JD, who practices in Kentucky, said this isn’t a problem since attorneys eventually must disclose the expert witnesses who will testify at trial.
“Knowing the name behind the certificate of merit is not that pertinent,” Mr. DeSimone said. “Physicians and their attorneys will ultimately have the chance to question and evaluate the expert witnesses used at trial. The certificate of merit is designed to weed out totally frivolous cases that do not have expert support. It’s not designed to be a trial on the merits.”
The belief that plaintiffs’ attorneys frequently bring weak cases and use unqualified experts to certify claims is not realistic or logical, added Sean Domnick, JD, a Florida medical malpractice attorney and vice president for the American Association for Justice. Medical malpractice cases are extremely challenging for plaintiffs – and they’re expensive, Mr. Domnick said.
“We can’t afford to take bad cases,” he said. “For me to take on a medical malpractice case, it’s not unusual for me to spend well over $100,000. Remember, if we lose, I don’t get that money back and I don’t get paid. Why in the world would a plaintiff take on that type of a burden for a case they didn’t believe in? The logic escapes me.”
In Florida, where Mr. Domnick practices, plaintiffs’ attorneys must send their certificates of merit to the defense with the expert identified. Domnick believes the requirement is a hindrance.
“It creates a delay that is unnecessary in a system that is already designed to wear our clients down,” he said. “It’s just another component that makes it harder on them.”
Hidden experts may insulate plaintiffs’ attorneys from liability
Dr. Sullivan, the Illinois emergency physician, was ultimately dismissed from the multiparty lawsuit, but not for roughly 18 months. After the dismissal, he fought back. He sued the plaintiff’s law firm for malicious prosecution, negligence in hiring, and relying on the opinion of an expert who was unqualified to render an opinion against an emergency physician.
The law firm, however, argued that it was immune from liability because it reasonably relied on the expert’s opinion as required by Illinois law. A trial court agreed with the plaintiffs’ firm. The judge denied Dr. Sullivan’s request to identify the expert, ruling there was no finding that the affidavit was untrue or made without reasonable cause. Dr. Sullivan appealed, and the appellate court upheld the trial’s court decision.
“As happened with my case, law firms can use the affidavit as a defense against countersuits or motions for sanctions,” Dr. Sullivan said. “Although the certificate of merit is intended to prevent attorneys from filing frivolous cases, it can also have the opposite effect of helping to insulate plaintiff attorneys from liability for filing a frivolous lawsuit.”
In Colorado, complaints about the state’s certificate of merit statute have gone before the Colorado Supreme Court. In one case, a lower court ruled that a certificate of merit was deficient because the consultants were not chiropractors. In another case, a nurse defendant argued the claim’s certificate of review was insufficient because the consulting expert was a physician.
In both instances, Colorado judges held the state’s statute does not require consultants to be in the same profession or the same specialty as the health professional defendant.
In New York, meanwhile, Mr. Auster said several bills to strengthen the state’s certificate of merit requirements have failed in recent years.
“It’s hard to say whether it will improve anytime soon,” he said. “The trial lawyers are a very powerful advocacy force in the state, and they tend to oppose even the slightest of changes in civil liability. [In addition], some of these issues have been put on a lower tier because of trying to manage the pandemic.”
Ultimately, Dr. Sullivan said that courts and legislatures need to strongly consider the ethics of allowing anonymous experts to provide testimony against defendant physicians.
“I also think we need to consider how the notion of a secret expert comports with a defendant physician’s due process,” he said. “If an expert’s opinion is appropriate, why would there be a need to shroud one’s identity in a veil of secrecy?”
A version of this article first appeared on Medscape.com.
When the hospital’s trauma team could not get an IV inserted into an accident victim, they called Illinois emergency physician William Sullivan, DO, JD, for help. Dr. Sullivan, who is based in the Chicago suburb of Frankfort, inserted a central line into the patient’s leg on his first attempt – a task that took about 20 minutes.
A year later, Dr. Sullivan was shocked and angry to learn he was being sued by the trauma patient’s family. Inserting the line was his only interaction with the woman, and he had no role in her care management, he said. Yet, the suit claimed he was negligent for failing to diagnose the patient with internal bleeding and for not performing surgery.
“The lawsuit put a lot of stress on our family,” Dr. Sullivan recalled. “At the time my wife was pregnant. I was in law school, and I was also working full time in the ER to support our family. I remember my wife crying on the couch after reading the complaint and asking how the plaintiff’s attorney could get away with making the allegations he made.”
Dr. Sullivan soon learned that 15 medical providers in the patient’s medical record were named as defendants. This included the director of the radiology department, whose name was on a radiology report as “director” but who was actually out of the country when the incident occurred.
Despite some of the accusations being impossible, a medical expert had claimed there was a “meritorious claim” against every health professional named in the suit. Illinois is among the 28 states that require plaintiffs’ attorneys to file an affidavit of merit for medical malpractice claims to move forward.
Dr. Sullivan wondered who would endorse such outlandish accusations, but the expert’s identity was a mystery. According to Illinois law, About one-third of states with merit requirements permit anonymous experts, according to research and attorneys familiar with the issue.
Because the expert’s identity remains hidden, physicians have no way of knowing whether they were qualified to render an opinion, Dr. Sullivan said. The loopholes can drag out frivolous claims and waste significant time and expense, say legal experts. Frequently, it takes a year or more before innocent physicians are dismissed from unfounded lawsuits by the court or dropped when plaintiffs can’t support the claim.
“It’s hugely frustrating,” said Bruce Montoya, JD, a Colorado medical liability defense attorney. “You have an expert who is not disclosed. Further down the road, when experts are being deposed, the plaintiff does not have to reveal whether any of those testifying experts is the same one who certified the case. You never get to determine whether they, in fact, had a certificate reviewer who was legitimate.”
The laws have led to a recent outcry among physicians and fueled a revised resolution by the American College of Emergency Physicians (ACEP) denouncing anonymous affidavits of merit. (The revision has not yet been published online.)
“The minute experts are identified, they can be vetted,” said Rade B. Vukmir, MD, JD, chair of ACEP’s Medical Legal Committee. “There are reasons that you want to clarify the qualification and veracity of the witness. [Anonymous affidavits of merit] don’t allow that, and there’s something inherently wrong with that.”
Because the identities of consulting experts are unknown, it’s hard to know how many are unqualified. Expert witnesses who testify during trials, on the other hand, have long come under scrutiny for questionable qualifications. Some have come under fire for allegedly lying under oath about their experience, misrepresenting their credentials, and falsely representing their knowledge.
“Considering the known problem of potentially unethical expert witness testimony at trial, there’s is the potential likelihood that experts in anonymous affidavits of merit may sometimes lack the qualifications to give opinions,” said Dr. Vukmir, an emergency care physician in Pittsburgh.
Attorneys: Hidden experts increase costs, waste time
In Colorado, Mr. Montoya has seen firsthand how anonymous experts can prolong questionable claims and burden defendants.
Like Illinois, Colorado does not require attorneys to identify the medical experts used to fulfill its certificate of review statute. The expert consulted must have expertise in the same area of the alleged negligence, but does not have to practice in the same specialty, and the statute allows one expert to certify a lawsuit against multiple doctors.
In a recent case, Mr. Montoya represented a Denver neurosurgeon who was sued along with multiple other health care professionals. From the outset, Mr. Montoya argued the claim had no merit against the neurosurgeon, but the plaintiff’s attorney refused to dismiss the physician. Mr. Montoya asked whether the expert consulted for the certificate of merit was a neurosurgeon, but the attorney declined to disclose that information, he said.
The case progressed and Mr. Montoya eventually asked the judge to review the certificate of merit. By law, a judge can confidentially review the certificate of merit and decide whether it aligns with the state statute, but without disclosing the expert’s identity to the defense. The judge ruled the certificate appeared to conform with state law, and the case continued.
A year later, as both sides were getting ready to disclose their experts who would testify, Mr. Montoya again argued the neurosurgeon should be dropped from the suit. This time, he warned if the claim continued against the neurosurgeon, the defense would be filing a motion for summary judgment and pursuing attorney fees and costs. Colorado law allows for such fees if the filing or pursuit of an action is frivolous.
“Boom, my client was dismissed,” Mr. Montoya said. “This is a year later, after multiple conferences among the attorneys, multiple pleadings filed, expert witnesses retained to review the care, discovery exchanged, and records obtained. If we had [a stronger] certificate of review statute, it would have been a different ballgame. It’s never going to get a year down the road.”
In New York, physician defendants have experienced similar woes. The state’s law requires plaintiffs’ attorneys to certify that they consulted with a physician prior to filing the claim, and that they believe based on that discussion, there’s a reasonable basis for the claim to move forward. Attorneys are not required to disclose the expert’s identity.
The law also allows “an out,” explained Morris Auster, JD, senior vice president and chief legislative counsel for the Medical Society of the State of New York. If the attorney made three separate attempts to obtain a consultation, and all three experts would not agree to the consultation, the lawsuit can be filed anyway, he said.
“From our standpoint, it’s important to have an affidavit of merit requirement; it’s better than not having it,” Mr. Auster said. “But its effectiveness in providing control over the filing of lawsuits in New York has never been as strong as it could’ve been.”
Mr. Auster notes that New York has some of the highest liability costs in the country in addition to doctors paying some of the steepest medical liability insurance premiums.
“This really affects a lot of physicians and it’s driving physicians into employment arrangements, so they don’t have to deal with it on their own,” he said. “We support a number of measures to address these significantly high costs, and stronger certificate of merit requirements would certainly be one of those advocacy goals.”
Why are anonymous experts allowed?
Certificates of merit that shield the identity of consultants encourage a greater pool of physicians willing to review cases, said J. Matthew Dudley, JD, president of the Illinois Trial Lawyers Association. When the requirements first went into effect in Illinois, there was significant animosity among physicians toward doctors who testified in medical malpractice cases for patients, Mr. Dudley explained.
“Sometimes they would be ostracized from their professional societies, or it would hurt a referral relationship.” he said. “Over time, that animosity has lessened, but there was a concern that if the identity of physicians in certificates of merit weren’t protected, then doctors would not look at cases for patients.”
This would result in additional barriers for patients and their attorneys in pursuing their legal rights, Mr. Dudley said. He said Illinois’ certificate of merit statute is successful in fulfilling its intended purpose, and he has not seen any statistical evidence to suggest otherwise.
“It has proven effective at decreasing filings in medical malpractice and effectively screening medical malpractice cases,” he said. “Certificates of merit help to decrease filings by firms that aren’t that experienced in dealing with those kinds of cases.”
Kentucky is another state that does not require attorneys to identity the experts consulted for certificates of merit. Malpractice defense attorney Andrew DeSimone, JD, who practices in Kentucky, said this isn’t a problem since attorneys eventually must disclose the expert witnesses who will testify at trial.
“Knowing the name behind the certificate of merit is not that pertinent,” Mr. DeSimone said. “Physicians and their attorneys will ultimately have the chance to question and evaluate the expert witnesses used at trial. The certificate of merit is designed to weed out totally frivolous cases that do not have expert support. It’s not designed to be a trial on the merits.”
The belief that plaintiffs’ attorneys frequently bring weak cases and use unqualified experts to certify claims is not realistic or logical, added Sean Domnick, JD, a Florida medical malpractice attorney and vice president for the American Association for Justice. Medical malpractice cases are extremely challenging for plaintiffs – and they’re expensive, Mr. Domnick said.
“We can’t afford to take bad cases,” he said. “For me to take on a medical malpractice case, it’s not unusual for me to spend well over $100,000. Remember, if we lose, I don’t get that money back and I don’t get paid. Why in the world would a plaintiff take on that type of a burden for a case they didn’t believe in? The logic escapes me.”
In Florida, where Mr. Domnick practices, plaintiffs’ attorneys must send their certificates of merit to the defense with the expert identified. Domnick believes the requirement is a hindrance.
“It creates a delay that is unnecessary in a system that is already designed to wear our clients down,” he said. “It’s just another component that makes it harder on them.”
Hidden experts may insulate plaintiffs’ attorneys from liability
Dr. Sullivan, the Illinois emergency physician, was ultimately dismissed from the multiparty lawsuit, but not for roughly 18 months. After the dismissal, he fought back. He sued the plaintiff’s law firm for malicious prosecution, negligence in hiring, and relying on the opinion of an expert who was unqualified to render an opinion against an emergency physician.
The law firm, however, argued that it was immune from liability because it reasonably relied on the expert’s opinion as required by Illinois law. A trial court agreed with the plaintiffs’ firm. The judge denied Dr. Sullivan’s request to identify the expert, ruling there was no finding that the affidavit was untrue or made without reasonable cause. Dr. Sullivan appealed, and the appellate court upheld the trial’s court decision.
“As happened with my case, law firms can use the affidavit as a defense against countersuits or motions for sanctions,” Dr. Sullivan said. “Although the certificate of merit is intended to prevent attorneys from filing frivolous cases, it can also have the opposite effect of helping to insulate plaintiff attorneys from liability for filing a frivolous lawsuit.”
In Colorado, complaints about the state’s certificate of merit statute have gone before the Colorado Supreme Court. In one case, a lower court ruled that a certificate of merit was deficient because the consultants were not chiropractors. In another case, a nurse defendant argued the claim’s certificate of review was insufficient because the consulting expert was a physician.
In both instances, Colorado judges held the state’s statute does not require consultants to be in the same profession or the same specialty as the health professional defendant.
In New York, meanwhile, Mr. Auster said several bills to strengthen the state’s certificate of merit requirements have failed in recent years.
“It’s hard to say whether it will improve anytime soon,” he said. “The trial lawyers are a very powerful advocacy force in the state, and they tend to oppose even the slightest of changes in civil liability. [In addition], some of these issues have been put on a lower tier because of trying to manage the pandemic.”
Ultimately, Dr. Sullivan said that courts and legislatures need to strongly consider the ethics of allowing anonymous experts to provide testimony against defendant physicians.
“I also think we need to consider how the notion of a secret expert comports with a defendant physician’s due process,” he said. “If an expert’s opinion is appropriate, why would there be a need to shroud one’s identity in a veil of secrecy?”
A version of this article first appeared on Medscape.com.
COVID booster mounts ‘brisk’ response in patients with cancer
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
New data shed light on the durability of antibody responses to SARS-CoV-2 vaccines and the impact of booster doses for patients with cancer undergoing systemic therapy or who have received a stem cell transplant (SCT).
In a cross-sectional study of 453 such patients, anti–SARS-CoV-2 spike protein receptor binding domain (anti-RBD) antibodies peaked 1 month after the second dose of an mRNA vaccine and remained stable over the next 6 months.
Notably, compared with the primary vaccine course, patients experienced a 20-fold increase in anti-RBD antibodies after the third vaccine dose, “indicative of a brisk anamnestic response from memory B cells,” Qamar Khan, MD, a medical oncologist at the University of Kansas Medical Center, Kansas City, and colleagues report.
The study appeared online in JAMA Oncology.
Given the risk of poor outcomes among patients with cancer and recipients of SCTs who get COVID, Dr. Khan and colleagues wanted to understand the durability of the antibody response to COVID vaccines in this population.
Among the 453 patients enrolled in the study, 70% had solid tumors and 30% had hematologic malignancies. Just over 40% were receiving chemotherapy, 16% were receiving immunotherapy, 14% were receiving a targeted oral agent, 5% were receiving chemoimmunotherapy, and 25% had received an SCT.
Regarding vaccine type, 61% received the Pfizer-BioNTech mRNA vaccine, 36% received the Moderna mRNA vaccine, and 4% got the Janssen/Johnson & Johnson vaccine. The mean age of the cohort was 60.4 years; 56% were women.
Prior to vaccination, the geometric mean titer (GMT) of anti-RBD antibodies for all patients was 1.7; it increased to 18.65 2 weeks after the first dose.
At 1 month after the second mRNA dose (or 2 months after the Johnson & Johnson vaccine), GMTs of anti-RBD antibodies reached 470.38 and then decreased to 425.8 at 3 months after the second dose (or 4 months after the Johnson & Johnson vaccine). Patients who were male, older than 65 years, and who had been diagnosed with a hematologic malignant tumor were more likely to have lower anti-RBD GMT 3 months after the second vaccine dose.
GMTs subsequently increased to 447.23 6 months after the second dose (7 months for Johnson & Johnson).
One month after the third dose, GMTs of anti-RBD antibodies rose to 9,224.85 – more than 20 times the previous GMT value.
According to the investigators, roughly 80% of these patients remained above the threshold of an anti-RBD level of 100 U/mL or higher at 6 months.
“While still an arbitrary cutoff, an anti-RBD level of 100 U/mL or higher has been associated with protection and has been used to evaluate the effectiveness of a third dose of an mRNA vaccine in a randomized clinical trial of patients who received a solid organ transplant,” Dr. Khan and colleagues write.
“Although more data are needed to confirm this level as protective, if established, anti-RBD can potentially be used to prioritize additional vaccine doses, especially in regions of the world with limited vaccine resources,” the authors conclude.
The study was supported in part by the University of Kansas Cancer Center and the Investigator Initiated Steering Committee, by a grant from the National Institute of General Medical Sciences, and a University of Kansas Cancer Center Support Grant from the National Cancer Institute. Dr. Khan reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA ONCOLOGY
Vegan diet helps shed pounds but doesn’t dint diabetes
on average, new research indicates.
No effect was seen on blood pressure, triglycerides, or high-density lipoprotein cholesterol. HbA1c was reduced by a mean of –0.18 percentage points (P = .002), and there was a small reduction in total cholesterol and low-density lipoprotein cholesterol, on average, across all the studies examined in this meta-analysis.
The work, which compared a number of trials looking at vegan diets versus “normal” eating or other kinds of weight loss diets, “indicates with reasonable certainty that adhering to a vegan diet for at least 12 weeks may result in clinically meaningful weight loss [and] can be used in the management of overweight and type 2 diabetes,” said Anne-Ditte Termannsen, PhD, who reported the findings during a press conference at the European Congress on Obesity 2022, where the work was also presented as a poster.
A vegan diet most likely led to weight loss because it is “associated with a reduced calorie intake due to a lower content of fat and higher content of dietary fiber,” added Dr. Termannsen of the Steno Diabetes Center Copenhagen.
Asked to comment, Janet Cade, PhD, who leads the Nutritional Epidemiology Group at the University of Leeds (England) said the results are likely attributable to fewer calories in the vegan diet, compared with the “control” diets. “Of course, a vegan diet can be healthier in a range of ways, such as higher fruit and vegetables, more fiber and antioxidants; however, the same would be true of a vegetarian diet,” she noted.
And she warned that longer-term data are needed on health outcomes associated with vegan diets, noting, “there have been links to poorer bone health and osteoporosis in people consuming a vegan diet.”
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England) told the UK Science Media Centre: “The authors conducted a systematic review of intervention studies and found that, compared with no dietary interventions, vegan diets showed the strongest association with body-weight reduction.”
However, “When comparing vegan diets with other dietary interventions – such as the Mediterranean diet – the association was much weaker,” he noted.
Vegan, habitual, or a range of weight-loss diets
Dr. Termannsen and colleagues set out to look at the effect of a plant-based diet on cardiometabolic risk factors in people with overweight or type 2 diabetes. They searched the literature for randomized controlled trials with adult participants with overweight (body mass index ≥ 25 kg/m2), prediabetes, or type 2 diabetes.
Participants followed a vegan diet that lasted at least 12 weeks; habitual diets without any changes or energy restriction; a Mediterranean diet; a host of different “diabetes” diets; a low-fat diet; or portion-controlled diets.
“The vegan diets were nearly all low-fat vegan diets but vary substantially regarding the protein, fat, carbohydrate content. All but one study was ad libitum fat, and there were no energy restrictions,” Dr. Termannsen said.
Control diets were more varied. “Some continued their habitual diet, and about half were energy restricted and the others were not,” she acknowledged.
Outcomes comprised body weight, BMI, HbA1c, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, which were assessed across studies.
A total of 11 trials were included in the meta-analysis, and studies were a mean duration of 19 weeks. A total of 796 participants were included.
Compared with control diets, those on vegan diets lost on average –4.1 kg (–9 lb) (P < .001), with a range of –5.9 kg to –2.4 kg.
BMI dropped by –1.38 kg/m2 (P < .001). Total cholesterol dropped by –0.30 mmol/L (–11.6 mg/dL; P = .007) and LDL cholesterol by –0.24 mmol/L (–9.28 mg/dL; P = .005).
Further analyses found even greater reductions in body weight and BMI when vegan diets were compared with continuing a normal diet without dietary changes, on average, at –7.4 kg (–16.3 lb) (P < .001) and –2.78 kg/m2 (P < .001) respectively.
When compared with other intervention diets, however, body weight dropped by –2.7 kg (–6 lb; P < .001) and BMI by –0.87 kg/m2 (P < .001).
Commenting on limitations of studies compared to the real world, Dr. Termannsen said: “Some studies reported high adherence to their diet, usually due to a high level of support, suggesting that providing continued face-to-face contact with participants may partly explain the adherence differences.”
“This also questions the long-term feasibility of the diet and the applicability of this as long-term care,” she added.
Following a vegan diet requires good planning to ensure adequate nutrition and avoid any deficiencies, she urged. “We need to remember that the menu plans in the studies were created by dietitians.”
A version of this article first appeared on Medscape.com.
on average, new research indicates.
No effect was seen on blood pressure, triglycerides, or high-density lipoprotein cholesterol. HbA1c was reduced by a mean of –0.18 percentage points (P = .002), and there was a small reduction in total cholesterol and low-density lipoprotein cholesterol, on average, across all the studies examined in this meta-analysis.
The work, which compared a number of trials looking at vegan diets versus “normal” eating or other kinds of weight loss diets, “indicates with reasonable certainty that adhering to a vegan diet for at least 12 weeks may result in clinically meaningful weight loss [and] can be used in the management of overweight and type 2 diabetes,” said Anne-Ditte Termannsen, PhD, who reported the findings during a press conference at the European Congress on Obesity 2022, where the work was also presented as a poster.
A vegan diet most likely led to weight loss because it is “associated with a reduced calorie intake due to a lower content of fat and higher content of dietary fiber,” added Dr. Termannsen of the Steno Diabetes Center Copenhagen.
Asked to comment, Janet Cade, PhD, who leads the Nutritional Epidemiology Group at the University of Leeds (England) said the results are likely attributable to fewer calories in the vegan diet, compared with the “control” diets. “Of course, a vegan diet can be healthier in a range of ways, such as higher fruit and vegetables, more fiber and antioxidants; however, the same would be true of a vegetarian diet,” she noted.
And she warned that longer-term data are needed on health outcomes associated with vegan diets, noting, “there have been links to poorer bone health and osteoporosis in people consuming a vegan diet.”
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England) told the UK Science Media Centre: “The authors conducted a systematic review of intervention studies and found that, compared with no dietary interventions, vegan diets showed the strongest association with body-weight reduction.”
However, “When comparing vegan diets with other dietary interventions – such as the Mediterranean diet – the association was much weaker,” he noted.
Vegan, habitual, or a range of weight-loss diets
Dr. Termannsen and colleagues set out to look at the effect of a plant-based diet on cardiometabolic risk factors in people with overweight or type 2 diabetes. They searched the literature for randomized controlled trials with adult participants with overweight (body mass index ≥ 25 kg/m2), prediabetes, or type 2 diabetes.
Participants followed a vegan diet that lasted at least 12 weeks; habitual diets without any changes or energy restriction; a Mediterranean diet; a host of different “diabetes” diets; a low-fat diet; or portion-controlled diets.
“The vegan diets were nearly all low-fat vegan diets but vary substantially regarding the protein, fat, carbohydrate content. All but one study was ad libitum fat, and there were no energy restrictions,” Dr. Termannsen said.
Control diets were more varied. “Some continued their habitual diet, and about half were energy restricted and the others were not,” she acknowledged.
Outcomes comprised body weight, BMI, HbA1c, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, which were assessed across studies.
A total of 11 trials were included in the meta-analysis, and studies were a mean duration of 19 weeks. A total of 796 participants were included.
Compared with control diets, those on vegan diets lost on average –4.1 kg (–9 lb) (P < .001), with a range of –5.9 kg to –2.4 kg.
BMI dropped by –1.38 kg/m2 (P < .001). Total cholesterol dropped by –0.30 mmol/L (–11.6 mg/dL; P = .007) and LDL cholesterol by –0.24 mmol/L (–9.28 mg/dL; P = .005).
Further analyses found even greater reductions in body weight and BMI when vegan diets were compared with continuing a normal diet without dietary changes, on average, at –7.4 kg (–16.3 lb) (P < .001) and –2.78 kg/m2 (P < .001) respectively.
When compared with other intervention diets, however, body weight dropped by –2.7 kg (–6 lb; P < .001) and BMI by –0.87 kg/m2 (P < .001).
Commenting on limitations of studies compared to the real world, Dr. Termannsen said: “Some studies reported high adherence to their diet, usually due to a high level of support, suggesting that providing continued face-to-face contact with participants may partly explain the adherence differences.”
“This also questions the long-term feasibility of the diet and the applicability of this as long-term care,” she added.
Following a vegan diet requires good planning to ensure adequate nutrition and avoid any deficiencies, she urged. “We need to remember that the menu plans in the studies were created by dietitians.”
A version of this article first appeared on Medscape.com.
on average, new research indicates.
No effect was seen on blood pressure, triglycerides, or high-density lipoprotein cholesterol. HbA1c was reduced by a mean of –0.18 percentage points (P = .002), and there was a small reduction in total cholesterol and low-density lipoprotein cholesterol, on average, across all the studies examined in this meta-analysis.
The work, which compared a number of trials looking at vegan diets versus “normal” eating or other kinds of weight loss diets, “indicates with reasonable certainty that adhering to a vegan diet for at least 12 weeks may result in clinically meaningful weight loss [and] can be used in the management of overweight and type 2 diabetes,” said Anne-Ditte Termannsen, PhD, who reported the findings during a press conference at the European Congress on Obesity 2022, where the work was also presented as a poster.
A vegan diet most likely led to weight loss because it is “associated with a reduced calorie intake due to a lower content of fat and higher content of dietary fiber,” added Dr. Termannsen of the Steno Diabetes Center Copenhagen.
Asked to comment, Janet Cade, PhD, who leads the Nutritional Epidemiology Group at the University of Leeds (England) said the results are likely attributable to fewer calories in the vegan diet, compared with the “control” diets. “Of course, a vegan diet can be healthier in a range of ways, such as higher fruit and vegetables, more fiber and antioxidants; however, the same would be true of a vegetarian diet,” she noted.
And she warned that longer-term data are needed on health outcomes associated with vegan diets, noting, “there have been links to poorer bone health and osteoporosis in people consuming a vegan diet.”
Gunter Kuhnle, PhD, professor of nutrition and food science, University of Reading (England) told the UK Science Media Centre: “The authors conducted a systematic review of intervention studies and found that, compared with no dietary interventions, vegan diets showed the strongest association with body-weight reduction.”
However, “When comparing vegan diets with other dietary interventions – such as the Mediterranean diet – the association was much weaker,” he noted.
Vegan, habitual, or a range of weight-loss diets
Dr. Termannsen and colleagues set out to look at the effect of a plant-based diet on cardiometabolic risk factors in people with overweight or type 2 diabetes. They searched the literature for randomized controlled trials with adult participants with overweight (body mass index ≥ 25 kg/m2), prediabetes, or type 2 diabetes.
Participants followed a vegan diet that lasted at least 12 weeks; habitual diets without any changes or energy restriction; a Mediterranean diet; a host of different “diabetes” diets; a low-fat diet; or portion-controlled diets.
“The vegan diets were nearly all low-fat vegan diets but vary substantially regarding the protein, fat, carbohydrate content. All but one study was ad libitum fat, and there were no energy restrictions,” Dr. Termannsen said.
Control diets were more varied. “Some continued their habitual diet, and about half were energy restricted and the others were not,” she acknowledged.
Outcomes comprised body weight, BMI, HbA1c, systolic and diastolic blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides, which were assessed across studies.
A total of 11 trials were included in the meta-analysis, and studies were a mean duration of 19 weeks. A total of 796 participants were included.
Compared with control diets, those on vegan diets lost on average –4.1 kg (–9 lb) (P < .001), with a range of –5.9 kg to –2.4 kg.
BMI dropped by –1.38 kg/m2 (P < .001). Total cholesterol dropped by –0.30 mmol/L (–11.6 mg/dL; P = .007) and LDL cholesterol by –0.24 mmol/L (–9.28 mg/dL; P = .005).
Further analyses found even greater reductions in body weight and BMI when vegan diets were compared with continuing a normal diet without dietary changes, on average, at –7.4 kg (–16.3 lb) (P < .001) and –2.78 kg/m2 (P < .001) respectively.
When compared with other intervention diets, however, body weight dropped by –2.7 kg (–6 lb; P < .001) and BMI by –0.87 kg/m2 (P < .001).
Commenting on limitations of studies compared to the real world, Dr. Termannsen said: “Some studies reported high adherence to their diet, usually due to a high level of support, suggesting that providing continued face-to-face contact with participants may partly explain the adherence differences.”
“This also questions the long-term feasibility of the diet and the applicability of this as long-term care,” she added.
Following a vegan diet requires good planning to ensure adequate nutrition and avoid any deficiencies, she urged. “We need to remember that the menu plans in the studies were created by dietitians.”
A version of this article first appeared on Medscape.com.
FROM ECO 2022