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What’s next for COVID? Here’s what to know
As holiday celebrations wind down in the United States, COVID is on the rise.
Cases, hospitalizations, deaths
As of Dec. 27, the latest statistics, the Centers for Disease Control and Prevention reports more than 487,000 weekly cases, compared to about 265,000 for the week ending Oct. 12. On average, 4,938 people were admitted to the hospital daily from Dec. 19 to 25, down about 6% from the 5,257 admitted daily the week before.
Deaths totaled 2,952 weekly as of Dec. 21, up from 2,699 on Dec. 14.
“What’s sobering overall is still seeing about 400 deaths a day in the U.S.,” said Peter Chin-Hong, MD, professor of medicine and infectious disease specialist at the University of California, San Francisco. “It’s still very high.”
As of Dec. 17, the variants predominating are BQ.1, BQ.1.1, and XBB. Experts said they are paying close attention to XBB, which is increasing quickly in the Northeast.
Predicting a winter surge
Experts tracking the pandemic agree there will be a surge.
“We are in the midst of it now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape (MDedge’s sister site). “It’s not nearly like what we’ve had in Omicron or other waves; it’s not as severe. But it’s being particularly felt by seniors.”
One bit of good news: “Outside of that group it doesn’t look like – so far – it is going to be as bad a wave [as in the past],” Dr. Topol said.
Predicting the extent of the post-holiday surge “is the billion-dollar question right now,” said Katelyn Jetelina, PhD, a San Diego epidemiologist and author of the newsletter Your Local Epidemiologist.
“Much of these waves are not being driven by subvariants of concern but rather behavior,” she said.
People are opening up their social networks to gather for celebrations and family time. That’s unique to this winter, she said.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
Others point out that the surge doesn’t involve just COVID.
“We are expecting a Christmas surge and we are concerned it might be a triple surge,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., referring to the rising cases of flu and RSV (respiratory syncytial virus).
Dr. Jetelina shares that concern, worrying that those illnesses may be what overwhelms hospital capacity.
Another wild card is the situation in China. With the easing of China’s “zero COVID” policies, cases there are rising dramatically. Some models are predicting up to 1 million COVID deaths could occur in China in 2023. (The United States is now requiring travelers from China to show a negative COVID test before entering. Italy and Japan have taken similar measures.)
“The suffering that is going to occur in China is not good news at all,” Dr. Topol said. “We are going to be seeing that for many weeks if not months ahead.”
Theoretically, uncontained spread such as what is expected there could generate a whole new family of variants, he said. But “the main hit is going to be in China,” he predicted. “But it’s hard to project with accuracy.”
“China is 20% of the global population, so we can’t ignore it,” Dr. Jetelina said. “The question is, what’s the probability of a subvariant of concern coming from China? I think the probability is pretty low, but the possibility is there.”
What happens with cases in China may “throw a wrench” in the transition from pandemic to endemic, Dr. Chin-Hong said. But even if the rising cases in China do result in a new variant, “there’s so much T cell and B cell immunity [here], your average person is still not going to get seriously ill, even if the variant looks really scary.”
Minimizing the damage
Experts echo the same advice on stemming the surge, especially for adults who are 65 or older: Get the bivalent booster, and get it now.
“The same with the influenza vaccine,” Dr. Schaffner said.
Both the booster vaccine and the flu vaccine have been underused this year, he said. “It’s part of the general vaccine fatigue.”
The low uptake of the booster vaccine is concerning, Dr. Topol said, especially among adults aged 65 and older, the age group most vulnerable to severe disease. Just 35.7% of U.S. adults 65 and older have gotten the booster, according to the CDC. Dr. Topol calls that a tragedy.
Younger people have not taken to the booster, either. Overall, only 14.1% of people aged 5 and up have gotten an updated booster dose, according to the CDC.
Recent studies find value in the boosters. One study looked only at adults age 65 or older, finding that the bivalent booster reduced the risk of hospitalization by 84% compared to someone not vaccinated, and 73% compared to someone who had received only the monovalent vaccine. Another study of adults found those who had gotten the bivalent were less likely to need COVID-related emergency room care or urgent care.
In a Dec. 21 report in the New England Journal of Medicine, researchers took plasma samples from people who had gotten either one or two monovalent boosters or the bivalent to determine how well they worked against the circulating Omicron subvariants BA.1, BA.5, BA.2.75.2, BQ.1.1, and XBB. The bivalent worked better than the monovalent against all the Omicron subvariants, but especially against BA.2.75.2, BQ.1.1, and XBB.
Rapid testing can help minimize transmission. On Dec. 15, the Biden administration announced its Winter Preparedness Plan, urging Americans to test before and after travel as well as indoor visiting with vulnerable individuals, providing another round of free at-home tests, continuing to make community testing available and continuing to provide vaccines.
Besides the general precautions, Dr. Schaffner suggested: “Look at yourself. Who are you? If you are older than 65, or have underlying illness or are immunocompromised, or are pregnant, please put your mask back on. And think about social distancing. It might be time to worship at home and stream a movie,” instead of going to the theaters, he said.
Back to mandates?
On Dec. 9, the New York City Commissioner of Health and Mental Hygiene urged a return to masking indoors, saying people “should” mask up, including in schools, stores, offices, and when in crowded outdoor settings.
On the same date, the County of Los Angeles Public Health urged a return to masking for everyone aged 2 and older when indoors, including at schools, in transit, or in work sites when around others.
While the CDC order requiring masks on public transportation is no longer in effect, the agency continues to recommend that those using public transportation do so.
But some are taking that further. In Philadelphia, for example, School Superintendent Tony B. Watlington Sr., EdD, announced before the winter break that indoor masking would be required for all students and staff for the first 2 weeks of school return, through Jan. 13, citing guidance from the Philadelphia Department of Public Health.
Universal masking in schools does reduce COVID transmission, as a study published in late November suggests. After Massachusetts dropped the statewide universal masking policy in public schools in February 2022, researchers compared the incidence of COVID in 70 school districts there that dropped the mandate with two school districts that kept it. In the 15 weeks after the policy was rescinded, the lifting of the mandate was linked with an additional 44.9 cases of COVID per 1,000 students and staff. That corresponded to an estimated 11,901 cases and to nearly 30% of the cases in all districts during that time.
That said, experts see mandates as the exception rather than the rule, at least for now, citing public backlash against mandates to mask or follow other restrictions.
“Mandating, we know, it shuts people off,” Dr. Topol said. “It’s unenforceable. If you have a very strong recommendation, that’s probably as good as you’re going to be able to do right now.”
There may be communities where mandates go over better than others, Dr. Schaffner said, such as communities where people have confidence in their public health authorities.
Glimmers of hope
Despite uncertainties, experts offered some not-so-dismal perspectives as well.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
A version of this article first appeared on WebMD.com.
As holiday celebrations wind down in the United States, COVID is on the rise.
Cases, hospitalizations, deaths
As of Dec. 27, the latest statistics, the Centers for Disease Control and Prevention reports more than 487,000 weekly cases, compared to about 265,000 for the week ending Oct. 12. On average, 4,938 people were admitted to the hospital daily from Dec. 19 to 25, down about 6% from the 5,257 admitted daily the week before.
Deaths totaled 2,952 weekly as of Dec. 21, up from 2,699 on Dec. 14.
“What’s sobering overall is still seeing about 400 deaths a day in the U.S.,” said Peter Chin-Hong, MD, professor of medicine and infectious disease specialist at the University of California, San Francisco. “It’s still very high.”
As of Dec. 17, the variants predominating are BQ.1, BQ.1.1, and XBB. Experts said they are paying close attention to XBB, which is increasing quickly in the Northeast.
Predicting a winter surge
Experts tracking the pandemic agree there will be a surge.
“We are in the midst of it now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape (MDedge’s sister site). “It’s not nearly like what we’ve had in Omicron or other waves; it’s not as severe. But it’s being particularly felt by seniors.”
One bit of good news: “Outside of that group it doesn’t look like – so far – it is going to be as bad a wave [as in the past],” Dr. Topol said.
Predicting the extent of the post-holiday surge “is the billion-dollar question right now,” said Katelyn Jetelina, PhD, a San Diego epidemiologist and author of the newsletter Your Local Epidemiologist.
“Much of these waves are not being driven by subvariants of concern but rather behavior,” she said.
People are opening up their social networks to gather for celebrations and family time. That’s unique to this winter, she said.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
Others point out that the surge doesn’t involve just COVID.
“We are expecting a Christmas surge and we are concerned it might be a triple surge,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., referring to the rising cases of flu and RSV (respiratory syncytial virus).
Dr. Jetelina shares that concern, worrying that those illnesses may be what overwhelms hospital capacity.
Another wild card is the situation in China. With the easing of China’s “zero COVID” policies, cases there are rising dramatically. Some models are predicting up to 1 million COVID deaths could occur in China in 2023. (The United States is now requiring travelers from China to show a negative COVID test before entering. Italy and Japan have taken similar measures.)
“The suffering that is going to occur in China is not good news at all,” Dr. Topol said. “We are going to be seeing that for many weeks if not months ahead.”
Theoretically, uncontained spread such as what is expected there could generate a whole new family of variants, he said. But “the main hit is going to be in China,” he predicted. “But it’s hard to project with accuracy.”
“China is 20% of the global population, so we can’t ignore it,” Dr. Jetelina said. “The question is, what’s the probability of a subvariant of concern coming from China? I think the probability is pretty low, but the possibility is there.”
What happens with cases in China may “throw a wrench” in the transition from pandemic to endemic, Dr. Chin-Hong said. But even if the rising cases in China do result in a new variant, “there’s so much T cell and B cell immunity [here], your average person is still not going to get seriously ill, even if the variant looks really scary.”
Minimizing the damage
Experts echo the same advice on stemming the surge, especially for adults who are 65 or older: Get the bivalent booster, and get it now.
“The same with the influenza vaccine,” Dr. Schaffner said.
Both the booster vaccine and the flu vaccine have been underused this year, he said. “It’s part of the general vaccine fatigue.”
The low uptake of the booster vaccine is concerning, Dr. Topol said, especially among adults aged 65 and older, the age group most vulnerable to severe disease. Just 35.7% of U.S. adults 65 and older have gotten the booster, according to the CDC. Dr. Topol calls that a tragedy.
Younger people have not taken to the booster, either. Overall, only 14.1% of people aged 5 and up have gotten an updated booster dose, according to the CDC.
Recent studies find value in the boosters. One study looked only at adults age 65 or older, finding that the bivalent booster reduced the risk of hospitalization by 84% compared to someone not vaccinated, and 73% compared to someone who had received only the monovalent vaccine. Another study of adults found those who had gotten the bivalent were less likely to need COVID-related emergency room care or urgent care.
In a Dec. 21 report in the New England Journal of Medicine, researchers took plasma samples from people who had gotten either one or two monovalent boosters or the bivalent to determine how well they worked against the circulating Omicron subvariants BA.1, BA.5, BA.2.75.2, BQ.1.1, and XBB. The bivalent worked better than the monovalent against all the Omicron subvariants, but especially against BA.2.75.2, BQ.1.1, and XBB.
Rapid testing can help minimize transmission. On Dec. 15, the Biden administration announced its Winter Preparedness Plan, urging Americans to test before and after travel as well as indoor visiting with vulnerable individuals, providing another round of free at-home tests, continuing to make community testing available and continuing to provide vaccines.
Besides the general precautions, Dr. Schaffner suggested: “Look at yourself. Who are you? If you are older than 65, or have underlying illness or are immunocompromised, or are pregnant, please put your mask back on. And think about social distancing. It might be time to worship at home and stream a movie,” instead of going to the theaters, he said.
Back to mandates?
On Dec. 9, the New York City Commissioner of Health and Mental Hygiene urged a return to masking indoors, saying people “should” mask up, including in schools, stores, offices, and when in crowded outdoor settings.
On the same date, the County of Los Angeles Public Health urged a return to masking for everyone aged 2 and older when indoors, including at schools, in transit, or in work sites when around others.
While the CDC order requiring masks on public transportation is no longer in effect, the agency continues to recommend that those using public transportation do so.
But some are taking that further. In Philadelphia, for example, School Superintendent Tony B. Watlington Sr., EdD, announced before the winter break that indoor masking would be required for all students and staff for the first 2 weeks of school return, through Jan. 13, citing guidance from the Philadelphia Department of Public Health.
Universal masking in schools does reduce COVID transmission, as a study published in late November suggests. After Massachusetts dropped the statewide universal masking policy in public schools in February 2022, researchers compared the incidence of COVID in 70 school districts there that dropped the mandate with two school districts that kept it. In the 15 weeks after the policy was rescinded, the lifting of the mandate was linked with an additional 44.9 cases of COVID per 1,000 students and staff. That corresponded to an estimated 11,901 cases and to nearly 30% of the cases in all districts during that time.
That said, experts see mandates as the exception rather than the rule, at least for now, citing public backlash against mandates to mask or follow other restrictions.
“Mandating, we know, it shuts people off,” Dr. Topol said. “It’s unenforceable. If you have a very strong recommendation, that’s probably as good as you’re going to be able to do right now.”
There may be communities where mandates go over better than others, Dr. Schaffner said, such as communities where people have confidence in their public health authorities.
Glimmers of hope
Despite uncertainties, experts offered some not-so-dismal perspectives as well.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
A version of this article first appeared on WebMD.com.
As holiday celebrations wind down in the United States, COVID is on the rise.
Cases, hospitalizations, deaths
As of Dec. 27, the latest statistics, the Centers for Disease Control and Prevention reports more than 487,000 weekly cases, compared to about 265,000 for the week ending Oct. 12. On average, 4,938 people were admitted to the hospital daily from Dec. 19 to 25, down about 6% from the 5,257 admitted daily the week before.
Deaths totaled 2,952 weekly as of Dec. 21, up from 2,699 on Dec. 14.
“What’s sobering overall is still seeing about 400 deaths a day in the U.S.,” said Peter Chin-Hong, MD, professor of medicine and infectious disease specialist at the University of California, San Francisco. “It’s still very high.”
As of Dec. 17, the variants predominating are BQ.1, BQ.1.1, and XBB. Experts said they are paying close attention to XBB, which is increasing quickly in the Northeast.
Predicting a winter surge
Experts tracking the pandemic agree there will be a surge.
“We are in the midst of it now,” said Eric Topol, MD, founder and director of the Scripps Research Translational Institute, La Jolla, Calif., and editor-in-chief of Medscape (MDedge’s sister site). “It’s not nearly like what we’ve had in Omicron or other waves; it’s not as severe. But it’s being particularly felt by seniors.”
One bit of good news: “Outside of that group it doesn’t look like – so far – it is going to be as bad a wave [as in the past],” Dr. Topol said.
Predicting the extent of the post-holiday surge “is the billion-dollar question right now,” said Katelyn Jetelina, PhD, a San Diego epidemiologist and author of the newsletter Your Local Epidemiologist.
“Much of these waves are not being driven by subvariants of concern but rather behavior,” she said.
People are opening up their social networks to gather for celebrations and family time. That’s unique to this winter, she said.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
Others point out that the surge doesn’t involve just COVID.
“We are expecting a Christmas surge and we are concerned it might be a triple surge,” said William Schaffner, MD, professor of infectious diseases at Vanderbilt University, Nashville, Tenn., referring to the rising cases of flu and RSV (respiratory syncytial virus).
Dr. Jetelina shares that concern, worrying that those illnesses may be what overwhelms hospital capacity.
Another wild card is the situation in China. With the easing of China’s “zero COVID” policies, cases there are rising dramatically. Some models are predicting up to 1 million COVID deaths could occur in China in 2023. (The United States is now requiring travelers from China to show a negative COVID test before entering. Italy and Japan have taken similar measures.)
“The suffering that is going to occur in China is not good news at all,” Dr. Topol said. “We are going to be seeing that for many weeks if not months ahead.”
Theoretically, uncontained spread such as what is expected there could generate a whole new family of variants, he said. But “the main hit is going to be in China,” he predicted. “But it’s hard to project with accuracy.”
“China is 20% of the global population, so we can’t ignore it,” Dr. Jetelina said. “The question is, what’s the probability of a subvariant of concern coming from China? I think the probability is pretty low, but the possibility is there.”
What happens with cases in China may “throw a wrench” in the transition from pandemic to endemic, Dr. Chin-Hong said. But even if the rising cases in China do result in a new variant, “there’s so much T cell and B cell immunity [here], your average person is still not going to get seriously ill, even if the variant looks really scary.”
Minimizing the damage
Experts echo the same advice on stemming the surge, especially for adults who are 65 or older: Get the bivalent booster, and get it now.
“The same with the influenza vaccine,” Dr. Schaffner said.
Both the booster vaccine and the flu vaccine have been underused this year, he said. “It’s part of the general vaccine fatigue.”
The low uptake of the booster vaccine is concerning, Dr. Topol said, especially among adults aged 65 and older, the age group most vulnerable to severe disease. Just 35.7% of U.S. adults 65 and older have gotten the booster, according to the CDC. Dr. Topol calls that a tragedy.
Younger people have not taken to the booster, either. Overall, only 14.1% of people aged 5 and up have gotten an updated booster dose, according to the CDC.
Recent studies find value in the boosters. One study looked only at adults age 65 or older, finding that the bivalent booster reduced the risk of hospitalization by 84% compared to someone not vaccinated, and 73% compared to someone who had received only the monovalent vaccine. Another study of adults found those who had gotten the bivalent were less likely to need COVID-related emergency room care or urgent care.
In a Dec. 21 report in the New England Journal of Medicine, researchers took plasma samples from people who had gotten either one or two monovalent boosters or the bivalent to determine how well they worked against the circulating Omicron subvariants BA.1, BA.5, BA.2.75.2, BQ.1.1, and XBB. The bivalent worked better than the monovalent against all the Omicron subvariants, but especially against BA.2.75.2, BQ.1.1, and XBB.
Rapid testing can help minimize transmission. On Dec. 15, the Biden administration announced its Winter Preparedness Plan, urging Americans to test before and after travel as well as indoor visiting with vulnerable individuals, providing another round of free at-home tests, continuing to make community testing available and continuing to provide vaccines.
Besides the general precautions, Dr. Schaffner suggested: “Look at yourself. Who are you? If you are older than 65, or have underlying illness or are immunocompromised, or are pregnant, please put your mask back on. And think about social distancing. It might be time to worship at home and stream a movie,” instead of going to the theaters, he said.
Back to mandates?
On Dec. 9, the New York City Commissioner of Health and Mental Hygiene urged a return to masking indoors, saying people “should” mask up, including in schools, stores, offices, and when in crowded outdoor settings.
On the same date, the County of Los Angeles Public Health urged a return to masking for everyone aged 2 and older when indoors, including at schools, in transit, or in work sites when around others.
While the CDC order requiring masks on public transportation is no longer in effect, the agency continues to recommend that those using public transportation do so.
But some are taking that further. In Philadelphia, for example, School Superintendent Tony B. Watlington Sr., EdD, announced before the winter break that indoor masking would be required for all students and staff for the first 2 weeks of school return, through Jan. 13, citing guidance from the Philadelphia Department of Public Health.
Universal masking in schools does reduce COVID transmission, as a study published in late November suggests. After Massachusetts dropped the statewide universal masking policy in public schools in February 2022, researchers compared the incidence of COVID in 70 school districts there that dropped the mandate with two school districts that kept it. In the 15 weeks after the policy was rescinded, the lifting of the mandate was linked with an additional 44.9 cases of COVID per 1,000 students and staff. That corresponded to an estimated 11,901 cases and to nearly 30% of the cases in all districts during that time.
That said, experts see mandates as the exception rather than the rule, at least for now, citing public backlash against mandates to mask or follow other restrictions.
“Mandating, we know, it shuts people off,” Dr. Topol said. “It’s unenforceable. If you have a very strong recommendation, that’s probably as good as you’re going to be able to do right now.”
There may be communities where mandates go over better than others, Dr. Schaffner said, such as communities where people have confidence in their public health authorities.
Glimmers of hope
Despite uncertainties, experts offered some not-so-dismal perspectives as well.
“I think our numbers will continue to go up, but certainly not like 2021 or 2020,” Dr. Chin-Hong said.
A version of this article first appeared on WebMD.com.
Even with insurance, EDs can cost a bundle
In 2019, the study shows, patients enrolled in big companies’ health plans paid an average of $646 in copays and deductibles for each ED visit. A quarter of visits cost more than $907 out of pocket, and another quarter cost under $128.
About half of households can’t afford to pay the average deductible in an employer-sponsored insurance plan, the report notes. And more than a third of U.S. adults are unable to afford a $400 medical expense without borrowing.
While it’s not known how many people don’t go to an emergency department because of the anticipated cost, almost half of U.S. adults report that they’ve delayed care because of costs, according to a recent Kaiser survey.
One problem that people often face when deciding whether to visit an ED is that they don’t know how serious their condition is and what emergency care will cost, says Hope Schwartz, lead author of the report.
“When they go to the [ED], they don’t always know what their diagnosis will be and what their treatment costs will be. What we highlighted is that those costs could be very high or very low, and there’s no way to tell beforehand,” she says.
What costs so much?
Based on the paid claims data used in the study, health plans and patients paid a combined average of $2,453 for an ER visit. A quarter of visits cost $970 or less, and a quarter cost $3,043 or more.
Emergency department claims include professional fees and facility fees. The facility fees, which cover the cost of a hospital maintaining an ED 24/7, made up 80% of total costs, including a portion of doctors’ claims as well as laboratory and imaging fees.
But doctors’ claims for evaluation and management services were the largest part of costs, averaging $1,134 per visit. Procedures and treatments cost over $1,100 per visit, on average, while the average imaging claim cost $483, and the average cost for lab work was $230.
More than half of visits generated imaging claims, and about half of visits included lab claims.
The Kaiser Family Foundation report also looked at the costs of several common ED diagnoses. The most expensive diagnosis was appendicitis, which cost nearly twice as much as heart attacks, partly because it often led to surgery in the emergency department. On average, a visit for appendicitis cost $9,535, of which $1,717 was an out-of-pocket expense.
In addition, the researchers examined lower-cost diagnoses that generally do not require imaging or extensive treatment in the ED. These included upper respiratory tract infections ($1,535 total, $523 out of pocket), skin and soft tissue infections ($2,005 total, $572 out of pocket), and urinary tract infections ($2,726 total, $683 out of pocket).
While these diagnoses can sometimes require admission to the hospital, in otherwise healthy adults they are typically evaluated with basic lab tests, and patients are discharged with prescriptions, according to the report.
Complexities of billing
ED visits are given codes to help show how complex the task or service was during the billing process. These codes have five levels.
Less complex visits require straightforward medical decision-making, such as rashes or medication refills. Patients with level 5 codes require highly complex decision-making and include life- or limb-threatening conditions, such as severe infections or heart attacks.
The less complex visits cost $592, on average, with patients responsible for $205 of that. For the most complex visits, the health plan covered $3,015, on average, or eight times the cost of the lowest-coded visits.
On average, patients paid $840 out of pocket for the most complex visits – four times the average costs for the less complex visits.
One reason for the rise in spending for ED visits is a national shift to higher-level ED billing codes, says Ms. Schwartz, who is a Kaiser Family Foundation health policy fellow and a medical student. “There has been good work done showing that [ED] visits are increasingly being billed as a level 4 or 5, whereas in previous years, they might have been billed as a level 3.
“Whether a hospital bills a level 4 or a level 5 code for your visit can make a really big difference in how much you pay. And if you come in not knowing what services you’re going to get, you don’t know if you’re going to get a level 3, 4, or 5 code, and the costs increase pretty quickly,” she says.
Costs vary by region
The report includes an analysis of emergency department costs in the 20 largest metropolitan areas in the United States. Overall, the researchers found, San Diego had the most expensive ED visits. Emergency departments in San Diego charged about twice as much per visit, on average, as those in Baltimore.
While there were expensive areas all across the country, many of the costliest places were in Texas, Florida, California, Colorado, and New York. The report noted that the most expensive regions for ED care did not align with the regions that had the most expensive health care overall.
“These comparisons suggest that our findings are not solely related to overall high health care prices in these areas and may reflect other factors, including the age and medical complexity of the population or differences in local norms and practice patterns,” the report says.
Healthier people
In addition to these geographical differences, the incidence of emergency department visits by those with employers’ insurance differed from that of the general population.
During the study year, the report found, 12% of the insured had at least one ED visit – a percentage that didn’t vary for any age group under 65, including children. (No patients 65 or older were included in the study.)
By comparison, a government survey shows that in 2019, 21% of all U.S. adults 18-44 had one or more emergency department visits. Among those 45-64, 20% made at least one ED visit.
A version of this article first appeared on WebMD.com.
In 2019, the study shows, patients enrolled in big companies’ health plans paid an average of $646 in copays and deductibles for each ED visit. A quarter of visits cost more than $907 out of pocket, and another quarter cost under $128.
About half of households can’t afford to pay the average deductible in an employer-sponsored insurance plan, the report notes. And more than a third of U.S. adults are unable to afford a $400 medical expense without borrowing.
While it’s not known how many people don’t go to an emergency department because of the anticipated cost, almost half of U.S. adults report that they’ve delayed care because of costs, according to a recent Kaiser survey.
One problem that people often face when deciding whether to visit an ED is that they don’t know how serious their condition is and what emergency care will cost, says Hope Schwartz, lead author of the report.
“When they go to the [ED], they don’t always know what their diagnosis will be and what their treatment costs will be. What we highlighted is that those costs could be very high or very low, and there’s no way to tell beforehand,” she says.
What costs so much?
Based on the paid claims data used in the study, health plans and patients paid a combined average of $2,453 for an ER visit. A quarter of visits cost $970 or less, and a quarter cost $3,043 or more.
Emergency department claims include professional fees and facility fees. The facility fees, which cover the cost of a hospital maintaining an ED 24/7, made up 80% of total costs, including a portion of doctors’ claims as well as laboratory and imaging fees.
But doctors’ claims for evaluation and management services were the largest part of costs, averaging $1,134 per visit. Procedures and treatments cost over $1,100 per visit, on average, while the average imaging claim cost $483, and the average cost for lab work was $230.
More than half of visits generated imaging claims, and about half of visits included lab claims.
The Kaiser Family Foundation report also looked at the costs of several common ED diagnoses. The most expensive diagnosis was appendicitis, which cost nearly twice as much as heart attacks, partly because it often led to surgery in the emergency department. On average, a visit for appendicitis cost $9,535, of which $1,717 was an out-of-pocket expense.
In addition, the researchers examined lower-cost diagnoses that generally do not require imaging or extensive treatment in the ED. These included upper respiratory tract infections ($1,535 total, $523 out of pocket), skin and soft tissue infections ($2,005 total, $572 out of pocket), and urinary tract infections ($2,726 total, $683 out of pocket).
While these diagnoses can sometimes require admission to the hospital, in otherwise healthy adults they are typically evaluated with basic lab tests, and patients are discharged with prescriptions, according to the report.
Complexities of billing
ED visits are given codes to help show how complex the task or service was during the billing process. These codes have five levels.
Less complex visits require straightforward medical decision-making, such as rashes or medication refills. Patients with level 5 codes require highly complex decision-making and include life- or limb-threatening conditions, such as severe infections or heart attacks.
The less complex visits cost $592, on average, with patients responsible for $205 of that. For the most complex visits, the health plan covered $3,015, on average, or eight times the cost of the lowest-coded visits.
On average, patients paid $840 out of pocket for the most complex visits – four times the average costs for the less complex visits.
One reason for the rise in spending for ED visits is a national shift to higher-level ED billing codes, says Ms. Schwartz, who is a Kaiser Family Foundation health policy fellow and a medical student. “There has been good work done showing that [ED] visits are increasingly being billed as a level 4 or 5, whereas in previous years, they might have been billed as a level 3.
“Whether a hospital bills a level 4 or a level 5 code for your visit can make a really big difference in how much you pay. And if you come in not knowing what services you’re going to get, you don’t know if you’re going to get a level 3, 4, or 5 code, and the costs increase pretty quickly,” she says.
Costs vary by region
The report includes an analysis of emergency department costs in the 20 largest metropolitan areas in the United States. Overall, the researchers found, San Diego had the most expensive ED visits. Emergency departments in San Diego charged about twice as much per visit, on average, as those in Baltimore.
While there were expensive areas all across the country, many of the costliest places were in Texas, Florida, California, Colorado, and New York. The report noted that the most expensive regions for ED care did not align with the regions that had the most expensive health care overall.
“These comparisons suggest that our findings are not solely related to overall high health care prices in these areas and may reflect other factors, including the age and medical complexity of the population or differences in local norms and practice patterns,” the report says.
Healthier people
In addition to these geographical differences, the incidence of emergency department visits by those with employers’ insurance differed from that of the general population.
During the study year, the report found, 12% of the insured had at least one ED visit – a percentage that didn’t vary for any age group under 65, including children. (No patients 65 or older were included in the study.)
By comparison, a government survey shows that in 2019, 21% of all U.S. adults 18-44 had one or more emergency department visits. Among those 45-64, 20% made at least one ED visit.
A version of this article first appeared on WebMD.com.
In 2019, the study shows, patients enrolled in big companies’ health plans paid an average of $646 in copays and deductibles for each ED visit. A quarter of visits cost more than $907 out of pocket, and another quarter cost under $128.
About half of households can’t afford to pay the average deductible in an employer-sponsored insurance plan, the report notes. And more than a third of U.S. adults are unable to afford a $400 medical expense without borrowing.
While it’s not known how many people don’t go to an emergency department because of the anticipated cost, almost half of U.S. adults report that they’ve delayed care because of costs, according to a recent Kaiser survey.
One problem that people often face when deciding whether to visit an ED is that they don’t know how serious their condition is and what emergency care will cost, says Hope Schwartz, lead author of the report.
“When they go to the [ED], they don’t always know what their diagnosis will be and what their treatment costs will be. What we highlighted is that those costs could be very high or very low, and there’s no way to tell beforehand,” she says.
What costs so much?
Based on the paid claims data used in the study, health plans and patients paid a combined average of $2,453 for an ER visit. A quarter of visits cost $970 or less, and a quarter cost $3,043 or more.
Emergency department claims include professional fees and facility fees. The facility fees, which cover the cost of a hospital maintaining an ED 24/7, made up 80% of total costs, including a portion of doctors’ claims as well as laboratory and imaging fees.
But doctors’ claims for evaluation and management services were the largest part of costs, averaging $1,134 per visit. Procedures and treatments cost over $1,100 per visit, on average, while the average imaging claim cost $483, and the average cost for lab work was $230.
More than half of visits generated imaging claims, and about half of visits included lab claims.
The Kaiser Family Foundation report also looked at the costs of several common ED diagnoses. The most expensive diagnosis was appendicitis, which cost nearly twice as much as heart attacks, partly because it often led to surgery in the emergency department. On average, a visit for appendicitis cost $9,535, of which $1,717 was an out-of-pocket expense.
In addition, the researchers examined lower-cost diagnoses that generally do not require imaging or extensive treatment in the ED. These included upper respiratory tract infections ($1,535 total, $523 out of pocket), skin and soft tissue infections ($2,005 total, $572 out of pocket), and urinary tract infections ($2,726 total, $683 out of pocket).
While these diagnoses can sometimes require admission to the hospital, in otherwise healthy adults they are typically evaluated with basic lab tests, and patients are discharged with prescriptions, according to the report.
Complexities of billing
ED visits are given codes to help show how complex the task or service was during the billing process. These codes have five levels.
Less complex visits require straightforward medical decision-making, such as rashes or medication refills. Patients with level 5 codes require highly complex decision-making and include life- or limb-threatening conditions, such as severe infections or heart attacks.
The less complex visits cost $592, on average, with patients responsible for $205 of that. For the most complex visits, the health plan covered $3,015, on average, or eight times the cost of the lowest-coded visits.
On average, patients paid $840 out of pocket for the most complex visits – four times the average costs for the less complex visits.
One reason for the rise in spending for ED visits is a national shift to higher-level ED billing codes, says Ms. Schwartz, who is a Kaiser Family Foundation health policy fellow and a medical student. “There has been good work done showing that [ED] visits are increasingly being billed as a level 4 or 5, whereas in previous years, they might have been billed as a level 3.
“Whether a hospital bills a level 4 or a level 5 code for your visit can make a really big difference in how much you pay. And if you come in not knowing what services you’re going to get, you don’t know if you’re going to get a level 3, 4, or 5 code, and the costs increase pretty quickly,” she says.
Costs vary by region
The report includes an analysis of emergency department costs in the 20 largest metropolitan areas in the United States. Overall, the researchers found, San Diego had the most expensive ED visits. Emergency departments in San Diego charged about twice as much per visit, on average, as those in Baltimore.
While there were expensive areas all across the country, many of the costliest places were in Texas, Florida, California, Colorado, and New York. The report noted that the most expensive regions for ED care did not align with the regions that had the most expensive health care overall.
“These comparisons suggest that our findings are not solely related to overall high health care prices in these areas and may reflect other factors, including the age and medical complexity of the population or differences in local norms and practice patterns,” the report says.
Healthier people
In addition to these geographical differences, the incidence of emergency department visits by those with employers’ insurance differed from that of the general population.
During the study year, the report found, 12% of the insured had at least one ED visit – a percentage that didn’t vary for any age group under 65, including children. (No patients 65 or older were included in the study.)
By comparison, a government survey shows that in 2019, 21% of all U.S. adults 18-44 had one or more emergency department visits. Among those 45-64, 20% made at least one ED visit.
A version of this article first appeared on WebMD.com.
Comorbidities and the prognosis of chronic obstructive pulmonary disease
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Strict control of comorbidities in patients with chronic obstructive pulmonary disease decreases exacerbations and morbimortality, and avoids readmissions. An increasing number of women have the disease, which progresses differently in women than in men and even has different comorbidities.
According to the scientific society’s press release, moderator María Gómez Antúnez, MD, stated, “The correct approach and treatment of these comorbidities is fundamental to improve the quality of life of the patient, decrease exacerbations, avoid readmissions, and decrease morbimortality in people with chronic obstructive pulmonary disease.”
The different works published, two of them by the SEMI COPD Working Group (ECCO and ESMI studies), indicate that the main comorbidities of patients with that pneumopathy are arterial hypertension, dyslipidemia, diabetes, heart failure, atrial fibrillation, ischemic heart disease, chronic kidney disease, peripheral arterial disease, and osteoporosis. Chronic hepatopathy, pulmonary neoplasm, depression, and cerebrovascular disease are less common.
73 comorbidities described
Dr. Alonso told this news organization, “Of those 73 comorbidities, some of the lesser known or less attention grabbing, according to a paper that we brought to the panel, include sleep disorders that encompass insomnia, nightmares, night terrors, sleep apneas, or hypopneas. Other lesser-known comorbidities related to cognitive decline, with patterns that reflect that up to 60% [of patients] may have some degree of deterioration, involve the disease phase, hypoxemia, or degree of inflammation. On the other hand, it has also been associated with Parkinson’s disease and gastroesophageal reflux, among many more that arise from the cardiovascular sphere.”
One paper reveals that more than 78% of patients with chronic obstructive pulmonary disease have one associated comorbidity, almost 69% have two, and 47.9% have three.
“Based on gender, comorbidities are different. In women, it is well observed that anxiety, depression, and osteoporosis are more common. However, hypertension, ischemic heart disease, and diabetes are more common in men with chronic obstructive pulmonary disease,” she stated.
“The pulmonary disease in question also progresses differently in men and women. In women, onset is at younger ages – between 40 and 50 years – and in men, after 50. Likewise, it appears that the disease progresses more quickly, which coincides with a worse quality of life (since dyspnea is tolerated less) and exceeds the anatomical differences, where hormonal influences play a dominant role,” Dr. Alonso stressed.
Reciprocal prognosis
Dr. Alonso stated, “The prognostic importance of comorbidities in the disease is reciprocal. In other words, if there are comorbidities that we do not look for or treat, they are going to have a negative influence on the chronic obstructive pulmonary disease. The disease will progress more and elevate the risk of exacerbations (the most important prognostic factor of that disease). In turn, if we are not treating the disease well, not only pharmacologically, it will have negative repercussions on the comorbidities. It will progress and have negative connotations, such as diabetes or ischemic heart disease.”
The aforementioned ECCO and ESMI studies include patients in internal medicine with exacerbations where the most common comorbidities have been mapped out, although there is also extensive research on comorbidities in patients who are admitted to departments other than internal medicine. “With regard to prognostic implications, our working group very clearly observed the comorbidities and the comorbidome, that solar system that appears so much in medical conferences and forums, which implies that proximity to the center of that solar system is related more to mortality, anxiety, depression, and breast cancer. Other pathologies, such as ischemic heart disease or dyslipidemia, are outside of that territory of greater risk, in which we have been more pioneering than other groups,” said Dr. Alonso.
The current trend is that the age of these patients is increasing, and there are more and more women with this pathology. According to the latest report from the Ministry of Health on respiratory diseases, the prevalence of chronic obstructive pulmonary disease among the population 40 years and older is around 33.9 cases per 1,000 inhabitants, more than twice as common in men than in women (47.7 vs. 21.3). Prevalence increases with age after 40 years progressively until reaching the greatest frequency in the 80- to 84-year-old age group.
In 2019, the number of deaths due to chronic obstructive pulmonary disease in Spain was 13,808 (9,907 men and 3,901 women), with a crude mortality rate of 29.3 deaths per 100,000 inhabitants. This toll decreased in comparison with that of 2018. Chronic obstructive pulmonary disease causes 2.5 times more deaths in men than in women. From 2001 to 2019, mortality due to that pathology declined by 43% in men and women. The decrease was almost 50% in men and 33% in women.
Overlap syndrome prevalent
Javier Sánchez Lora, MD, of the internal medicine department of the Virgen de la Victoria de Málaga University Clinical Hospital, discussed chronic obstructive pulmonary disease and sleep disorders. More concretely, he spoke about overlap syndrome: chronic obstructive pulmonary disease plus obstructive sleep apnea. According to the international consensus document on obstructive sleep apnea, the diagnosis requires an apnea-hypopnea index (AHI) equal to or greater than 15 per hour or equal to or greater than 5. The patient must also have one or more of the following factors: excessive daytime sleepiness, sleep that is not restful, excessive fatigue, and deterioration in quality of life related to sleep and not justified by other causes.
“The overlap syndrome affects 3%-66% of chronic obstructive pulmonary diseases and 7%-55% of obstructive sleep apnea,” said Dr. Sánchez Lora. This syndrome has important effects on different systems: at the cardiovascular level (arterial and pulmonary hypertension, heart failure, stroke, arrhythmias, ischemic heart disease, pulmonary thromboembolism), metabolic (insulin resistance, diabetes, metabolic syndrome), neurocognitive (dementia, depression), and neoplastic (lung, pancreas, esophagus) effects.
“These patients have a worse prognosis than those that have these pathologies alone. During sleep, they experience more frequent episodes of oxygen desaturation and they have a longer total period of sleep with hypoxemia and hypercapnia than those with obstructive apnea alone without chronic obstructive pulmonary disease,” said Dr. Sánchez Lora.
The apneic events of patients with the syndrome have a more profound hypoxemia and more arrhythmias, in addition to them being more susceptible to developing pulmonary hypertension than those with chronic obstructive pulmonary disease or sleep apnea alone. “The good news is that in patients with overlap, the use of ventilation with positive pressure reduces all causes of hospitalization and the visits to the emergency room, as well as the moderate and severe exacerbations of the disease.”
Dr. Sánchez Lora referred to a series of recommendations in clinical practice for the diagnosis and treatment of overlap syndrome: screening, combined therapy of hygienic-dietary measures, and the use of continuous positive respiratory pressure. Oxygen therapy to correct isolated nocturnal desaturations has not shown benefits in survival, although a benefit trial of symptoms attributed to nocturnal hypoxemia in patients with significant comorbidity can be conducted.
Underdiagnosis
“During the panel, we also spoke about the importance that as part of internal medicine we need to make an effort to reduce the underdiagnosis of chronic pulmonary disease and its comorbidities. Specialists in internal medicine need to become aware that this pathology is not only pulmonary, but also multisystemic, complex, heterogenous, and very variable even in the same patient,” said Dr. Sánchez Lora.
Dr. Alonso said, “Regarding the importance of diagnosis of this disease, we continue with an underdiagnosis greater than 70% for men and 80% for women. Secondly, we need to actively seek out the comorbidities associated with chronic obstructive pulmonary disease, even taking advantage of the admission of these patients with exacerbations, which are undesired and common.
“Regarding ongoing trials, we have a study that started during the COVID-19 pandemic, ADEG-EPOC, that involves the adaptation to and impact of severe and very severe exacerbations in patients admitted to our departments,” the specialist indicated.
“In the group, we are also planning to publish an updated agreement, which we already made in 2014, on the most common and important comorbidities associated with chronic obstructive pulmonary disease.” The agreement discusses the 20 most important comorbidities. In addition, the 2023 Gold Guide, which appeared in November 2022, includes a new chapter on updated treatment and the latest developments.
In the last 5 years, Dr. Alonso has collaborated with Abbott, AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, Ferrer, Fresenius Kabi, GSK, Nestlé, Novo Nordisk, Nutricia, and Menarini. Dr. Sánchez Lora has collaborated with AstraZeneca, Boehringer Ingelheim, Chiesi, FAES, GSK, and Menarini.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
Findings question value of pessary for pelvic organ prolapse
The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found.
Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.
Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.
Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.
“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.
She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.
The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.
“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.
After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.
Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.
However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.
The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.
But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.
Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”
Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”
Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”
The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.
A version of this article first appeared on Medscape.com.
The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found.
Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.
Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.
Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.
“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.
She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.
The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.
“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.
After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.
Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.
However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.
The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.
But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.
Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”
Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”
Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”
The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.
A version of this article first appeared on Medscape.com.
The standard nonsurgical treatment for pelvic organ prolapse does not appear to work as well as surgery to correct the problem, Dutch researchers have found.
Pelvic organ prolapse is an uncomfortable condition, causing a troublesome vaginal bulge, often accompanied by urinary, bowel, or sexual dysfunction. Between 3% and 6% of women develop symptomatic prolapse, with the highest incidence in women aged 60-69 years – a fast-growing demographic.
Although many women choose surgical treatment, the American College of Obstetricians and Gynecologists recommends that women be offered a vaginal pessary as a noninvasive alternative, despite inconsistent data from observational studies on their effectiveness.
Lisa van der Vaart, MD, a doctoral student in ob.gyn. at the University of Amsterdam and the lead author of the new study, published in JAMA, said that differences in outcome measures, small sample size, and lack of long-term follow-up have bedeviled previous comparisons of the two techniques.
“We thought it was very important to perform a randomized control trial on this subject to improve counseling to women who suffer from symptomatic pelvic organ prolapse,” Dr. van der Vaart said.
She and her colleagues conducted a noninferiority randomized clinical trial that recruited 1,605 women with stage II or higher prolapse who were referred to specialty care at 21 hospitals in the Netherlands between 2015 and 2019. Of the 440 women who agreed to participate in the trial, 218 received a pessary, a device inserted into the vagina that provides support to tissues displaced by prolapse, and 222 underwent surgery.
The primary outcome was subjective improvement using a standardized questionnaire at 24 months; women were asked to rank their symptoms on a seven-point scale, and subjective improvement was defined as a response of much better or very much better.
“We saw a substantial amount of improvement in both groups,” Dr. van der Vaart said in an interview.
After 24 months of follow-up, outcome data were available for 173 women in the pessary group and 162 in the surgery group. For this intention-to treat population, 76.3% in the pessary group and 81.5% in the surgery group reported improvement.
Results were similar for the smaller group of participants who completed the study per protocol, without crossing over to a treatment to which they had not been allocated.
However, neither the intention-to-treat nor per-protocol analysis met the prespecified criteria for noninferiority, suggesting that use of a vaginal pessary is not equivalent to surgery.
The study also found differences in adverse events. Among women randomly assigned to surgery, 9% suffered a postoperative urinary tract infection, and 5.4% underwent additional therapy, such as pessary or repeat operation.
But use of a pessary also had downsides. The most common adverse event was discomfort (42.7%), and by 24 months, 60% of the participants in the pessary group had discontinued use.
Dr. van der Vaart said that she was surprised by the high number of women assigned to the pessary group who later elected to undergo surgery. “Women should be told that their chance of crossing over to a surgical intervention is quite high – more than 50% do eventually end up having surgery.”
Cheryl Iglesia, MD, director of the National Center for Advanced Pelvic Surgery at MedStar Health and professor of obstetrics and gynecology and urology at Georgetown University, both in Washington, was also struck by the high crossover rate. “We’ve had the same pessaries probably for the last 100 years,” she said. “We need to get better.”
Dr. Iglesia welcomed new approaches to making vaginal pessaries that are custom designed for each woman’s unique anatomy using 3D printing and pointed to promising initial clinical trials of disposable pessaries. With the aging of the population and demand for treatment of prolapse increasing, she cited a need for better nonsurgical alternatives: “We have a work-force issue and may not have enough adequately trained urogynecologists to meet the demand for prolapse repairs as our population ages.”
The study was funded by a grant from ZonMW, a Dutch governmental health care organization. Dr. van der Vaart reported grants from ZonMW during the conduct of the study.
A version of this article first appeared on Medscape.com.
FROM JAMA
Medical practice gave 8,000 patients cancer for Christmas
We wish you a merry Christmas and a happy heart failure
Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.
Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.
It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.
One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
Genes know it: You are when you eat
There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.
The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.
The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.
Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
This group practice reduced stress for everyone
It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.
Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”
By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.
After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.
Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”
Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”
Who needs to make up stuff? Not us.
We wish you a merry Christmas and a happy heart failure
Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.
Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.
It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.
One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
Genes know it: You are when you eat
There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.
The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.
The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.
Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
This group practice reduced stress for everyone
It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.
Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”
By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.
After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.
Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”
Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”
Who needs to make up stuff? Not us.
We wish you a merry Christmas and a happy heart failure
Does anyone really like it when places of business send out cards or messages for the holidays? A card from a truly small family business is one thing, but when you start getting emails from multibillion dollar corporations, it feels a bit dishonest. And that’s not even mentioning the potential blowback when things go wrong.
Now, you may wonder how a company could possibly mess up something so simple. “We wish you a merry Christmas and a happy New Year.” Not that difficult. Unless you’re Askern Medical Practice in Doncaster, England. Instead of expressing a simple expression of joy for the holiday season, Askern informed all 8,000 of its patients that they had aggressive lung cancer with metastases and they needed to fill out a DS1500 form, which entitles terminal patients to certain benefits.
It only took an hour for Askern to recognize its mistake and send a second text apologizing and adding in the appropriate season’s greetings, but obviously the damage was done. Presumably patients who were last at the doctor to have their cold treated were able to shrug off the text, or simply didn’t see it before the correction came through, but obviously many patients had concerns directly related to cancer and panicked. They called in but were by and large unable to reach anyone at the practice. Some patients close by even went to center itself to clear things up.
One patient, Mr. Carl Chegwin, raised an excellent point about the debacle: “What if that message was meant for someone, and then they are told it’s a Christmas message, then again told, ‘Oh no, that was actually meant for you?’ ” The old double backtrack into yes, you actually do have cancer has got to be a candidate for worst Christmas gift of all. Yes, even worse than socks.
Genes know it: You are when you eat
There’s been a lot of recent research on intermittent fasting and what it can and can’t do for one’s health. Much of it has focused on participants’ metabolic rates, but a study just published in Cell Metabolism shows how time-restricted feeding (TRF) has an impact on gene expression, the process through which genes are activated and respond to their environment by creating proteins.
The research conducted by Satchidananda Panda, PhD, of the Salk Institute and his team involved two groups of mice, one with free access to food and the other with a daily 9-hour feeding window. Analysis of tissue samples collected from 22 organ groups revealed that nearly 80% of mouse genes responded to TRF. Interestingly, 40% of the genes in the hypothalamus, adrenal gland, and pancreas, which handle hormone regulation, were affected, suggesting that TRF could potentially aid in diabetes and stress disorder management, the investigators said in a written statement.
The researchers also found that TRF aligned the circadian rhythms of multiple organs of the body, which brings sleep into the picture. “Time-restricted eating synchronized the circadian rhythms to have two major waves: one during fasting, and another just after eating. We suspect this allows the body to coordinate different processes,” said Dr. Panda, whose previous research looked at TRF in firefighters, who typically work on shift schedules.
Time-restricted eating, it appears, affects gene expression throughout the body and allows interconnected organ systems to work smoothly. It’s not just about eating. Go figure.
This group practice reduced stress for everyone
It’s been awhile since we checked in on the good folks at Maharishi International University in Fairfield, Iowa – fictional home of the Fighting Transcendentalists [MAHARISHI RULES!] – but we just have to mention their long-term effort to reduce the national stress.
Way back in the year 2000, a group from MIU began practicing transcendental meditation. The size of the group increased over the next few years and eventually reached 1,725 in 2006. That number is important because it represents the square root of 1% of the U.S. population. When that “transition threshold was achieved,” the university explained in a written statement, “all stress indicators immediately started decreasing.”
By stress indicators they mean the U.S. stress index, the mean of eight variables – murder, rape, assault, robbery, infant mortality, drug deaths, vehicle fatalities, and child deaths by injuries – that the study investigators used to track the effectiveness of the meditation program, they said in the World Journal of Social Science.
After 2011, “when the size of the group size began to decline the rate of decrease in stress slowed and then it reversed and began to increase,” MIU reported.
Coauthor Dr. Kenneth Cavanaugh of MIU explained the process: “This study used state-of-the-art methods of time series regression analysis for eliminating potential alternative explanations due to intrinsic preexisting trends and fluctuations in the data. We carefully studied potential alternative explanations in terms of changes in economic conditions, political leadership, population demographics, and policing strategies. None of these factors could account for the results.”
Since we here at LOTME are serious professional journalists, the use of quotes means we are not making this up. Here’s one more thing in quotes: “A grant for 75 million dollars from the Howard and Alice Settle Foundation provided stipends for participants to be in the group and provided funding to bring several hundred visiting [meditation] experts from India to further augment the MIU group.”
Who needs to make up stuff? Not us.
Oral Propranolol Used as Adjunct Therapy in Cutaneous Angiosarcoma
To the Editor:
Angiosarcoma is a malignancy of the vascular endothelium that most commonly presents on the skin.1 Patients diagnosed with cutaneous angiosarcoma, which is a rare and aggressive malignancy, have a 5-year survival rate of approximately 30%.2,3 Angiosarcoma can be seen in the setting of chronic lymphedema; radiation therapy; and sporadically in elderly patients, where it is commonly seen on the head and neck. Presentation on the head and neck has been associated with worse outcomes, with a projected overall 10-year survival rate of 13.8%; the survival rate is lower if the tumor is surgically unresectable or larger in size. Metastasis can occur via both lymphatic and hematogenous routes, with pulmonary and hepatic metastases most frequently observed.1 Prognostications of poor outcomes for patients with head and neck cutaneous angiosarcoma via a 5-year survival rate were identified in a meta-analysis and included the following: patient age older than 70 years, larger tumors, tumor location of scalp vs face, nonsurgical treatments, and lack of clear margins on histology.2
Treatment of angiosarcoma historically has encompassed both surgical resection and adjuvant radiation therapy with suboptimal success. Evidence supporting various treatment regimens remains sparse due to the low incidence of the neoplasm. Although surgical resection is the only documented curative treatment, cutaneous angiosarcomas frequently are found to have positive surgical margins and require adjuvant radiation. Use of high-dose radiation (>50 Gy) with application over a wide treatment area such as total scalp irradiation is recommended.4 Although radiation has been found to diminish local recurrence rates, it has not substantially affected rates of distant disease recurrence.1 Cytotoxic chemotherapy has clinical utility in minimizing progression, but standard regimens afford a progression-free survival of only months.3 Adjuvant treatment with paclitaxel has been shown to have improved efficacy in scalp angiosarcoma vs other visceral sites, showing a nonprogression rate of 42% at 4 months after treatment.5 More recently, targeted chemotherapeutics, including the vascular endothelial growth factor inhibitor bevacizumab and tyrosine kinase inhibitor sorafenib, have shown some survival benefit, but it is unclear if these agents are superior to traditional cytotoxic agents.4,6-10 A phase 2 study of paclitaxel administered weekly with or without bevacizumab showed similar progression-free survival and overall survival, albeit at the expense of added toxicity experienced by participants in the combined group.10
The addition of the nonselective β-adrenergic blocker propranolol to the treatment armamentarium, which was pursued due to its utility in the treatment of benign infantile hemangioma and demonstrated ability to limit the expression of adrenergic receptors in angiosarcoma, has gained clinical attention for possible augmentation of cutaneous angiosarcoma therapy.11-14 Propranolol has been shown to reduce metastasis in other neoplasms—both vascular and nonvascular—and may play a role as an adjuvant treatment to current therapies in angiosarcoma.15-20 We report a patient with cutaneous angiosarcoma (T2 classification) with disease-free survival of nearly 6 years without evidence of recurrence in the setting of continuous propranolol use supplementary to chemotherapy and radiation.
A 78-year-old man with a history of multiple basal cell carcinomas, hypertension, and remote smoking history presented to the dermatology clinic with an enlarging red-brown plaque on the scalp of 2 months’ duration. The lesion had grown rapidly to involve the forehead, right temple, preauricular region, and parietal scalp. At presentation, the tumor measured more than 20 cm in diameter at its greatest point (Figure 1). Physical examination revealed a 6-mm purple nodule within the lesion on the patient’s right parietal scalp. No clinical lymphadenopathy was appreciated at the time of diagnosis. Punch biopsies of the right parietal scalp nodule and right temple patch showed findings consistent with angiosarcoma with diffuse cytoplasmic staining of CD31 in atypical endothelial cells and no staining for human herpesvirus 8 (Figure 2). Concurrent computed tomography of the head showed thickening of the right epidermis, dermis, and deeper scalp tissues, but there was no evidence of skull involvement. Computed tomography of the thorax, abdomen, and pelvis showed no evidence of metastatic disease. After a diagnostic workup, the patient was diagnosed with T2bN0M0 angiosarcoma.
The lesion was determined to be nonresectable due to the extent of the patient’s cutaneous disease. The patient was started on a regimen of paclitaxel, scalp radiation, and oral propranolol. Propranolol 40 mg twice daily was initiated at the time of diagnosis with a plan to continue indefinitely. Starting 1 month after staging, the patient completed 10 weekly cycles of paclitaxel, and he was treated with 60 Gy of scalp radiation in 30 fractions, starting with the second cycle of paclitaxel. He tolerated both well with no reported adverse events. Repeat computed tomography performed 1 month after completion of chemotherapy and radiation showed no evidence of a mass or fluid collection in subcutaneous scalp tissues and no evidence of metastatic disease. This correlated with an observed clinical regression at 1 month and complete clinical response at 5 months with residual hemosiderin and radiation changes. The area of prior disease involvement subsequently evolved from violet to dusky gray in appearance to an eventual complete resolution 26 months after diagnosis, accompanied by atrophic radiation-induced sequelae (Figure 3).
The patient’s postchemotherapy course was complicated by hospitalization for a suspected malignant pleural effusion. Analysis revealed growing ground-glass opacities and nodules in the right lower lung lobe. A thoracentesis with cytology studies was negative for malignancy. Continued monitoring over 19 months demonstrated eventual resolution of those findings. He experienced notable complication from local radiation therapy to the scalp with chronic cutaneous ulceration refractory to wound care and surgical intervention. The patient did not exhibit additional signs or symptoms concerning for recurrence or metastasis and was followed by dermatology and oncology until he died nearly 5 years after initial diagnosis due to complications from acute hypoxic respiratory failure secondary to COVID-19. The last imaging obtained showed no convincing evidence of metastasis, though spinal imaging within a month of his death showed lesions favored to represent benign angiomatous growths. His survival after diagnosis ultimately reached 57 months without confirmed disease recurrence and cause of death unrelated to malignancy history, which is a markedly long documented survival for this extent of disease.
Cutaneous angiosarcoma is an aggressive yet rare malignancy without effective treatments for prolonging survival or eradicating disease. Cutaneous angiosarcoma of the head and neck has a reported 10-year survival rate of 13.8%.1 Although angiosarcoma in any location holds a bleak prognosis, cutaneous angiosarcoma of the scalp with a T2 classification has a 2-year survival rate of 0%. Moreover, even if remission is achieved, disease is highly recurrent, typically within months with the current standard of care.3,21,22
Emerging evidence for the possible role of β-adrenergic receptor blockade in the treatment of malignant vascular neoplasms is promising. Microarrays from a host of vascular growths have demonstrated expression of β-adrenergic receptors in 77% of sampled angiosarcoma specimens in addition to strong expression in infantile hemangiomas, hemangiomas, hemangioendotheliomas, and vascular malformations.19 Research findings have further verified the validity of this approach with the demonstration of b1-, b2-, and b3- adrenergic receptor expression by angiosarcoma cell lines. Propranolol subsequently was shown to effectively target proliferation of these cells and induce apoptosis in a dose-dependent manner and moreover be synergistic in effect with other chemotherapies.15 Several genes have exhibited differential expression between control tumor cells and propranolol-treated cells. Specifically, target genes including AXL (a receptor tyrosine kinase associated with cell adhesion, proliferation, and apoptosis and found to upregulated in melanoma and leukemia) and ERBB receptor feedback inhibitor 1 (receptor tyrosine kinase, with ERBB family members commonly overexpressed or mutated in the setting malignancy) have been posited as possible explanatory factors in the observed angiosarcoma response to propranolol.23
Several cases describing propranolol use as an adjunctive therapy for angiosarcoma suggest a beneficial role in clinical medicine. One case report described propranolol monotherapy for lesion to our patient, with a resultant reduction in Ki-67 as a measure of proliferative index within 1 week of initiating propranolol therapy.13 Propranolol also has been shown to halt or slow progression of metastatic disease in visceral and metastatic angiosarcomas.12-14 In combination with oral etoposide and cyclophosphamide, maintenance propranolol therapy in 7 cases of advanced cutaneous angiosarcoma resulted in 1 complete response and 3 very good partial responses, with a median progression-free survival of 11 months.11 Larger-scale studies have not been published, but the growing number of case reports and case series warrants further investigation of the utility of propranolol as an adjunct to current therapies in advanced angiosarcoma.
- Abraham JA, Hornicek FJ, Kaufman AM, et al. Treatment and outcome of 82 patients with angiosarcoma. Ann Surg Oncol. 2007;14:1953-1967.
- Shin JY, Roh SG, Lee NH, et al. Predisposing factors for poor prognosis of angiosarcoma of the scalp and face: systematic review and meta-analysis. Head Neck. 2017;39:380-386.
- Fury MG, Antonescu CR, Zee KJV, et al. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer. 2005;11:241-247.
- Dossett LA, Harrington M, Cruse CW, et al. Cutaneous angiosarcoma. Curr Probl Cancer. 2015;39:258-263.
- Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008;26:5269-5274.
- Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013;24:257-263.
- Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27:3133-3140.
- Ishida Y, Otsuka A, Kabashima K. Cutaneous angiosarcoma: update on biology and latest treatment. Curr Opin Oncol. 2018;30:107-112.
- Ray-Coquard I, Italiano A, Bompas E, et al. Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist. 2012;17:260-266.
- Ray-Coquard IL, Domont J, Tresch-Bruneel E, et al. Paclitaxel given once per week with or without bevacizumab in patients with advanced angiosarcoma: a randomized phase II trial. J Clin Oncol. 2015;33:2797-2802.
- Pasquier E, Andre N, Street J, et al. Effective management of advanced angiosarcoma by the synergistic combination of propranolol and vinblastine-based metronomic chemotherapy: a bench to bedside study. EBioMedicine. 2016;6:87-95.
- Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience. 2015;9:499.
- Chow W, Amaya CN, Rains S, et al. Growth attenuation of cutaneous angiosarcoma with propranolol-mediated beta-blockade. JAMA Dermatol. 2015;151:1226-1229.
- Daguze J, Saint-Jean M, Peuvrel L, et al. Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. JAAD Case Rep. 2016;2:497-499.
- Stiles JM, Amaya C, Rains S, et al. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PLoS One. 2013;8:e60021.
- Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: a nationwide population-based study. PLoS One. 2019;14:e0216828.
- De Giorgi V, Grazzini M, Benemei S, et al. Propranolol for off-label treatment of patients with melanoma: results from a cohort study. JAMA Oncol. 2018;4:e172908.
- Rico M, Baglioni M, Bondarenko M, et al. Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models. Oncotarget. 2017;8:2874-2889.
- Chisholm KM, Chang KW, Truong MT, et al. β-Adrenergic receptor expression in vascular tumors. Mod Pathol. 2012;25:1446-1451.
- Leaute-Labreze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358:2649-2651.
- Maddox JC, Evans HL. Angiosarcoma of skin and soft tissue: a study of forty-four cases. Cancer. 1981;48:1907-1921.
- Morgan MB, Swann M, Somach S, et al. Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol. 2004;50:867-874.
- Zhou S, Liu P, Jiang W, et al. Identification of potential target genes associated with the effect of propranolol on angiosarcoma via microarray analysis. Oncol Lett. 2017;13:4267-4275.
To the Editor:
Angiosarcoma is a malignancy of the vascular endothelium that most commonly presents on the skin.1 Patients diagnosed with cutaneous angiosarcoma, which is a rare and aggressive malignancy, have a 5-year survival rate of approximately 30%.2,3 Angiosarcoma can be seen in the setting of chronic lymphedema; radiation therapy; and sporadically in elderly patients, where it is commonly seen on the head and neck. Presentation on the head and neck has been associated with worse outcomes, with a projected overall 10-year survival rate of 13.8%; the survival rate is lower if the tumor is surgically unresectable or larger in size. Metastasis can occur via both lymphatic and hematogenous routes, with pulmonary and hepatic metastases most frequently observed.1 Prognostications of poor outcomes for patients with head and neck cutaneous angiosarcoma via a 5-year survival rate were identified in a meta-analysis and included the following: patient age older than 70 years, larger tumors, tumor location of scalp vs face, nonsurgical treatments, and lack of clear margins on histology.2
Treatment of angiosarcoma historically has encompassed both surgical resection and adjuvant radiation therapy with suboptimal success. Evidence supporting various treatment regimens remains sparse due to the low incidence of the neoplasm. Although surgical resection is the only documented curative treatment, cutaneous angiosarcomas frequently are found to have positive surgical margins and require adjuvant radiation. Use of high-dose radiation (>50 Gy) with application over a wide treatment area such as total scalp irradiation is recommended.4 Although radiation has been found to diminish local recurrence rates, it has not substantially affected rates of distant disease recurrence.1 Cytotoxic chemotherapy has clinical utility in minimizing progression, but standard regimens afford a progression-free survival of only months.3 Adjuvant treatment with paclitaxel has been shown to have improved efficacy in scalp angiosarcoma vs other visceral sites, showing a nonprogression rate of 42% at 4 months after treatment.5 More recently, targeted chemotherapeutics, including the vascular endothelial growth factor inhibitor bevacizumab and tyrosine kinase inhibitor sorafenib, have shown some survival benefit, but it is unclear if these agents are superior to traditional cytotoxic agents.4,6-10 A phase 2 study of paclitaxel administered weekly with or without bevacizumab showed similar progression-free survival and overall survival, albeit at the expense of added toxicity experienced by participants in the combined group.10
The addition of the nonselective β-adrenergic blocker propranolol to the treatment armamentarium, which was pursued due to its utility in the treatment of benign infantile hemangioma and demonstrated ability to limit the expression of adrenergic receptors in angiosarcoma, has gained clinical attention for possible augmentation of cutaneous angiosarcoma therapy.11-14 Propranolol has been shown to reduce metastasis in other neoplasms—both vascular and nonvascular—and may play a role as an adjuvant treatment to current therapies in angiosarcoma.15-20 We report a patient with cutaneous angiosarcoma (T2 classification) with disease-free survival of nearly 6 years without evidence of recurrence in the setting of continuous propranolol use supplementary to chemotherapy and radiation.
A 78-year-old man with a history of multiple basal cell carcinomas, hypertension, and remote smoking history presented to the dermatology clinic with an enlarging red-brown plaque on the scalp of 2 months’ duration. The lesion had grown rapidly to involve the forehead, right temple, preauricular region, and parietal scalp. At presentation, the tumor measured more than 20 cm in diameter at its greatest point (Figure 1). Physical examination revealed a 6-mm purple nodule within the lesion on the patient’s right parietal scalp. No clinical lymphadenopathy was appreciated at the time of diagnosis. Punch biopsies of the right parietal scalp nodule and right temple patch showed findings consistent with angiosarcoma with diffuse cytoplasmic staining of CD31 in atypical endothelial cells and no staining for human herpesvirus 8 (Figure 2). Concurrent computed tomography of the head showed thickening of the right epidermis, dermis, and deeper scalp tissues, but there was no evidence of skull involvement. Computed tomography of the thorax, abdomen, and pelvis showed no evidence of metastatic disease. After a diagnostic workup, the patient was diagnosed with T2bN0M0 angiosarcoma.
The lesion was determined to be nonresectable due to the extent of the patient’s cutaneous disease. The patient was started on a regimen of paclitaxel, scalp radiation, and oral propranolol. Propranolol 40 mg twice daily was initiated at the time of diagnosis with a plan to continue indefinitely. Starting 1 month after staging, the patient completed 10 weekly cycles of paclitaxel, and he was treated with 60 Gy of scalp radiation in 30 fractions, starting with the second cycle of paclitaxel. He tolerated both well with no reported adverse events. Repeat computed tomography performed 1 month after completion of chemotherapy and radiation showed no evidence of a mass or fluid collection in subcutaneous scalp tissues and no evidence of metastatic disease. This correlated with an observed clinical regression at 1 month and complete clinical response at 5 months with residual hemosiderin and radiation changes. The area of prior disease involvement subsequently evolved from violet to dusky gray in appearance to an eventual complete resolution 26 months after diagnosis, accompanied by atrophic radiation-induced sequelae (Figure 3).
The patient’s postchemotherapy course was complicated by hospitalization for a suspected malignant pleural effusion. Analysis revealed growing ground-glass opacities and nodules in the right lower lung lobe. A thoracentesis with cytology studies was negative for malignancy. Continued monitoring over 19 months demonstrated eventual resolution of those findings. He experienced notable complication from local radiation therapy to the scalp with chronic cutaneous ulceration refractory to wound care and surgical intervention. The patient did not exhibit additional signs or symptoms concerning for recurrence or metastasis and was followed by dermatology and oncology until he died nearly 5 years after initial diagnosis due to complications from acute hypoxic respiratory failure secondary to COVID-19. The last imaging obtained showed no convincing evidence of metastasis, though spinal imaging within a month of his death showed lesions favored to represent benign angiomatous growths. His survival after diagnosis ultimately reached 57 months without confirmed disease recurrence and cause of death unrelated to malignancy history, which is a markedly long documented survival for this extent of disease.
Cutaneous angiosarcoma is an aggressive yet rare malignancy without effective treatments for prolonging survival or eradicating disease. Cutaneous angiosarcoma of the head and neck has a reported 10-year survival rate of 13.8%.1 Although angiosarcoma in any location holds a bleak prognosis, cutaneous angiosarcoma of the scalp with a T2 classification has a 2-year survival rate of 0%. Moreover, even if remission is achieved, disease is highly recurrent, typically within months with the current standard of care.3,21,22
Emerging evidence for the possible role of β-adrenergic receptor blockade in the treatment of malignant vascular neoplasms is promising. Microarrays from a host of vascular growths have demonstrated expression of β-adrenergic receptors in 77% of sampled angiosarcoma specimens in addition to strong expression in infantile hemangiomas, hemangiomas, hemangioendotheliomas, and vascular malformations.19 Research findings have further verified the validity of this approach with the demonstration of b1-, b2-, and b3- adrenergic receptor expression by angiosarcoma cell lines. Propranolol subsequently was shown to effectively target proliferation of these cells and induce apoptosis in a dose-dependent manner and moreover be synergistic in effect with other chemotherapies.15 Several genes have exhibited differential expression between control tumor cells and propranolol-treated cells. Specifically, target genes including AXL (a receptor tyrosine kinase associated with cell adhesion, proliferation, and apoptosis and found to upregulated in melanoma and leukemia) and ERBB receptor feedback inhibitor 1 (receptor tyrosine kinase, with ERBB family members commonly overexpressed or mutated in the setting malignancy) have been posited as possible explanatory factors in the observed angiosarcoma response to propranolol.23
Several cases describing propranolol use as an adjunctive therapy for angiosarcoma suggest a beneficial role in clinical medicine. One case report described propranolol monotherapy for lesion to our patient, with a resultant reduction in Ki-67 as a measure of proliferative index within 1 week of initiating propranolol therapy.13 Propranolol also has been shown to halt or slow progression of metastatic disease in visceral and metastatic angiosarcomas.12-14 In combination with oral etoposide and cyclophosphamide, maintenance propranolol therapy in 7 cases of advanced cutaneous angiosarcoma resulted in 1 complete response and 3 very good partial responses, with a median progression-free survival of 11 months.11 Larger-scale studies have not been published, but the growing number of case reports and case series warrants further investigation of the utility of propranolol as an adjunct to current therapies in advanced angiosarcoma.
To the Editor:
Angiosarcoma is a malignancy of the vascular endothelium that most commonly presents on the skin.1 Patients diagnosed with cutaneous angiosarcoma, which is a rare and aggressive malignancy, have a 5-year survival rate of approximately 30%.2,3 Angiosarcoma can be seen in the setting of chronic lymphedema; radiation therapy; and sporadically in elderly patients, where it is commonly seen on the head and neck. Presentation on the head and neck has been associated with worse outcomes, with a projected overall 10-year survival rate of 13.8%; the survival rate is lower if the tumor is surgically unresectable or larger in size. Metastasis can occur via both lymphatic and hematogenous routes, with pulmonary and hepatic metastases most frequently observed.1 Prognostications of poor outcomes for patients with head and neck cutaneous angiosarcoma via a 5-year survival rate were identified in a meta-analysis and included the following: patient age older than 70 years, larger tumors, tumor location of scalp vs face, nonsurgical treatments, and lack of clear margins on histology.2
Treatment of angiosarcoma historically has encompassed both surgical resection and adjuvant radiation therapy with suboptimal success. Evidence supporting various treatment regimens remains sparse due to the low incidence of the neoplasm. Although surgical resection is the only documented curative treatment, cutaneous angiosarcomas frequently are found to have positive surgical margins and require adjuvant radiation. Use of high-dose radiation (>50 Gy) with application over a wide treatment area such as total scalp irradiation is recommended.4 Although radiation has been found to diminish local recurrence rates, it has not substantially affected rates of distant disease recurrence.1 Cytotoxic chemotherapy has clinical utility in minimizing progression, but standard regimens afford a progression-free survival of only months.3 Adjuvant treatment with paclitaxel has been shown to have improved efficacy in scalp angiosarcoma vs other visceral sites, showing a nonprogression rate of 42% at 4 months after treatment.5 More recently, targeted chemotherapeutics, including the vascular endothelial growth factor inhibitor bevacizumab and tyrosine kinase inhibitor sorafenib, have shown some survival benefit, but it is unclear if these agents are superior to traditional cytotoxic agents.4,6-10 A phase 2 study of paclitaxel administered weekly with or without bevacizumab showed similar progression-free survival and overall survival, albeit at the expense of added toxicity experienced by participants in the combined group.10
The addition of the nonselective β-adrenergic blocker propranolol to the treatment armamentarium, which was pursued due to its utility in the treatment of benign infantile hemangioma and demonstrated ability to limit the expression of adrenergic receptors in angiosarcoma, has gained clinical attention for possible augmentation of cutaneous angiosarcoma therapy.11-14 Propranolol has been shown to reduce metastasis in other neoplasms—both vascular and nonvascular—and may play a role as an adjuvant treatment to current therapies in angiosarcoma.15-20 We report a patient with cutaneous angiosarcoma (T2 classification) with disease-free survival of nearly 6 years without evidence of recurrence in the setting of continuous propranolol use supplementary to chemotherapy and radiation.
A 78-year-old man with a history of multiple basal cell carcinomas, hypertension, and remote smoking history presented to the dermatology clinic with an enlarging red-brown plaque on the scalp of 2 months’ duration. The lesion had grown rapidly to involve the forehead, right temple, preauricular region, and parietal scalp. At presentation, the tumor measured more than 20 cm in diameter at its greatest point (Figure 1). Physical examination revealed a 6-mm purple nodule within the lesion on the patient’s right parietal scalp. No clinical lymphadenopathy was appreciated at the time of diagnosis. Punch biopsies of the right parietal scalp nodule and right temple patch showed findings consistent with angiosarcoma with diffuse cytoplasmic staining of CD31 in atypical endothelial cells and no staining for human herpesvirus 8 (Figure 2). Concurrent computed tomography of the head showed thickening of the right epidermis, dermis, and deeper scalp tissues, but there was no evidence of skull involvement. Computed tomography of the thorax, abdomen, and pelvis showed no evidence of metastatic disease. After a diagnostic workup, the patient was diagnosed with T2bN0M0 angiosarcoma.
The lesion was determined to be nonresectable due to the extent of the patient’s cutaneous disease. The patient was started on a regimen of paclitaxel, scalp radiation, and oral propranolol. Propranolol 40 mg twice daily was initiated at the time of diagnosis with a plan to continue indefinitely. Starting 1 month after staging, the patient completed 10 weekly cycles of paclitaxel, and he was treated with 60 Gy of scalp radiation in 30 fractions, starting with the second cycle of paclitaxel. He tolerated both well with no reported adverse events. Repeat computed tomography performed 1 month after completion of chemotherapy and radiation showed no evidence of a mass or fluid collection in subcutaneous scalp tissues and no evidence of metastatic disease. This correlated with an observed clinical regression at 1 month and complete clinical response at 5 months with residual hemosiderin and radiation changes. The area of prior disease involvement subsequently evolved from violet to dusky gray in appearance to an eventual complete resolution 26 months after diagnosis, accompanied by atrophic radiation-induced sequelae (Figure 3).
The patient’s postchemotherapy course was complicated by hospitalization for a suspected malignant pleural effusion. Analysis revealed growing ground-glass opacities and nodules in the right lower lung lobe. A thoracentesis with cytology studies was negative for malignancy. Continued monitoring over 19 months demonstrated eventual resolution of those findings. He experienced notable complication from local radiation therapy to the scalp with chronic cutaneous ulceration refractory to wound care and surgical intervention. The patient did not exhibit additional signs or symptoms concerning for recurrence or metastasis and was followed by dermatology and oncology until he died nearly 5 years after initial diagnosis due to complications from acute hypoxic respiratory failure secondary to COVID-19. The last imaging obtained showed no convincing evidence of metastasis, though spinal imaging within a month of his death showed lesions favored to represent benign angiomatous growths. His survival after diagnosis ultimately reached 57 months without confirmed disease recurrence and cause of death unrelated to malignancy history, which is a markedly long documented survival for this extent of disease.
Cutaneous angiosarcoma is an aggressive yet rare malignancy without effective treatments for prolonging survival or eradicating disease. Cutaneous angiosarcoma of the head and neck has a reported 10-year survival rate of 13.8%.1 Although angiosarcoma in any location holds a bleak prognosis, cutaneous angiosarcoma of the scalp with a T2 classification has a 2-year survival rate of 0%. Moreover, even if remission is achieved, disease is highly recurrent, typically within months with the current standard of care.3,21,22
Emerging evidence for the possible role of β-adrenergic receptor blockade in the treatment of malignant vascular neoplasms is promising. Microarrays from a host of vascular growths have demonstrated expression of β-adrenergic receptors in 77% of sampled angiosarcoma specimens in addition to strong expression in infantile hemangiomas, hemangiomas, hemangioendotheliomas, and vascular malformations.19 Research findings have further verified the validity of this approach with the demonstration of b1-, b2-, and b3- adrenergic receptor expression by angiosarcoma cell lines. Propranolol subsequently was shown to effectively target proliferation of these cells and induce apoptosis in a dose-dependent manner and moreover be synergistic in effect with other chemotherapies.15 Several genes have exhibited differential expression between control tumor cells and propranolol-treated cells. Specifically, target genes including AXL (a receptor tyrosine kinase associated with cell adhesion, proliferation, and apoptosis and found to upregulated in melanoma and leukemia) and ERBB receptor feedback inhibitor 1 (receptor tyrosine kinase, with ERBB family members commonly overexpressed or mutated in the setting malignancy) have been posited as possible explanatory factors in the observed angiosarcoma response to propranolol.23
Several cases describing propranolol use as an adjunctive therapy for angiosarcoma suggest a beneficial role in clinical medicine. One case report described propranolol monotherapy for lesion to our patient, with a resultant reduction in Ki-67 as a measure of proliferative index within 1 week of initiating propranolol therapy.13 Propranolol also has been shown to halt or slow progression of metastatic disease in visceral and metastatic angiosarcomas.12-14 In combination with oral etoposide and cyclophosphamide, maintenance propranolol therapy in 7 cases of advanced cutaneous angiosarcoma resulted in 1 complete response and 3 very good partial responses, with a median progression-free survival of 11 months.11 Larger-scale studies have not been published, but the growing number of case reports and case series warrants further investigation of the utility of propranolol as an adjunct to current therapies in advanced angiosarcoma.
- Abraham JA, Hornicek FJ, Kaufman AM, et al. Treatment and outcome of 82 patients with angiosarcoma. Ann Surg Oncol. 2007;14:1953-1967.
- Shin JY, Roh SG, Lee NH, et al. Predisposing factors for poor prognosis of angiosarcoma of the scalp and face: systematic review and meta-analysis. Head Neck. 2017;39:380-386.
- Fury MG, Antonescu CR, Zee KJV, et al. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer. 2005;11:241-247.
- Dossett LA, Harrington M, Cruse CW, et al. Cutaneous angiosarcoma. Curr Probl Cancer. 2015;39:258-263.
- Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008;26:5269-5274.
- Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013;24:257-263.
- Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27:3133-3140.
- Ishida Y, Otsuka A, Kabashima K. Cutaneous angiosarcoma: update on biology and latest treatment. Curr Opin Oncol. 2018;30:107-112.
- Ray-Coquard I, Italiano A, Bompas E, et al. Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist. 2012;17:260-266.
- Ray-Coquard IL, Domont J, Tresch-Bruneel E, et al. Paclitaxel given once per week with or without bevacizumab in patients with advanced angiosarcoma: a randomized phase II trial. J Clin Oncol. 2015;33:2797-2802.
- Pasquier E, Andre N, Street J, et al. Effective management of advanced angiosarcoma by the synergistic combination of propranolol and vinblastine-based metronomic chemotherapy: a bench to bedside study. EBioMedicine. 2016;6:87-95.
- Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience. 2015;9:499.
- Chow W, Amaya CN, Rains S, et al. Growth attenuation of cutaneous angiosarcoma with propranolol-mediated beta-blockade. JAMA Dermatol. 2015;151:1226-1229.
- Daguze J, Saint-Jean M, Peuvrel L, et al. Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. JAAD Case Rep. 2016;2:497-499.
- Stiles JM, Amaya C, Rains S, et al. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PLoS One. 2013;8:e60021.
- Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: a nationwide population-based study. PLoS One. 2019;14:e0216828.
- De Giorgi V, Grazzini M, Benemei S, et al. Propranolol for off-label treatment of patients with melanoma: results from a cohort study. JAMA Oncol. 2018;4:e172908.
- Rico M, Baglioni M, Bondarenko M, et al. Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models. Oncotarget. 2017;8:2874-2889.
- Chisholm KM, Chang KW, Truong MT, et al. β-Adrenergic receptor expression in vascular tumors. Mod Pathol. 2012;25:1446-1451.
- Leaute-Labreze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358:2649-2651.
- Maddox JC, Evans HL. Angiosarcoma of skin and soft tissue: a study of forty-four cases. Cancer. 1981;48:1907-1921.
- Morgan MB, Swann M, Somach S, et al. Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol. 2004;50:867-874.
- Zhou S, Liu P, Jiang W, et al. Identification of potential target genes associated with the effect of propranolol on angiosarcoma via microarray analysis. Oncol Lett. 2017;13:4267-4275.
- Abraham JA, Hornicek FJ, Kaufman AM, et al. Treatment and outcome of 82 patients with angiosarcoma. Ann Surg Oncol. 2007;14:1953-1967.
- Shin JY, Roh SG, Lee NH, et al. Predisposing factors for poor prognosis of angiosarcoma of the scalp and face: systematic review and meta-analysis. Head Neck. 2017;39:380-386.
- Fury MG, Antonescu CR, Zee KJV, et al. A 14-year retrospective review of angiosarcoma: clinical characteristics, prognostic factors, and treatment outcomes with surgery and chemotherapy. Cancer. 2005;11:241-247.
- Dossett LA, Harrington M, Cruse CW, et al. Cutaneous angiosarcoma. Curr Probl Cancer. 2015;39:258-263.
- Penel N, Bui BN, Bay JO, et al. Phase II trial of weekly paclitaxel for unresectable angiosarcoma: the ANGIOTAX study. J Clin Oncol. 2008;26:5269-5274.
- Agulnik M, Yarber JL, Okuno SH, et al. An open-label, multicenter, phase II study of bevacizumab for the treatment of angiosarcoma and epithelioid hemangioendotheliomas. Ann Oncol. 2013;24:257-263.
- Maki RG, D’Adamo DR, Keohan ML, et al. Phase II study of sorafenib in patients with metastatic or recurrent sarcomas. J Clin Oncol. 2009;27:3133-3140.
- Ishida Y, Otsuka A, Kabashima K. Cutaneous angiosarcoma: update on biology and latest treatment. Curr Opin Oncol. 2018;30:107-112.
- Ray-Coquard I, Italiano A, Bompas E, et al. Sorafenib for patients with advanced angiosarcoma: a phase II trial from the French Sarcoma Group (GSF/GETO). Oncologist. 2012;17:260-266.
- Ray-Coquard IL, Domont J, Tresch-Bruneel E, et al. Paclitaxel given once per week with or without bevacizumab in patients with advanced angiosarcoma: a randomized phase II trial. J Clin Oncol. 2015;33:2797-2802.
- Pasquier E, Andre N, Street J, et al. Effective management of advanced angiosarcoma by the synergistic combination of propranolol and vinblastine-based metronomic chemotherapy: a bench to bedside study. EBioMedicine. 2016;6:87-95.
- Banavali S, Pasquier E, Andre N. Targeted therapy with propranolol and metronomic chemotherapy combination: sustained complete response of a relapsing metastatic angiosarcoma. Ecancermedicalscience. 2015;9:499.
- Chow W, Amaya CN, Rains S, et al. Growth attenuation of cutaneous angiosarcoma with propranolol-mediated beta-blockade. JAMA Dermatol. 2015;151:1226-1229.
- Daguze J, Saint-Jean M, Peuvrel L, et al. Visceral metastatic angiosarcoma treated effectively with oral cyclophosphamide combined with propranolol. JAAD Case Rep. 2016;2:497-499.
- Stiles JM, Amaya C, Rains S, et al. Targeting of beta adrenergic receptors results in therapeutic efficacy against models of hemangioendothelioma and angiosarcoma. PLoS One. 2013;8:e60021.
- Chang PY, Chung CH, Chang WC, et al. The effect of propranolol on the prognosis of hepatocellular carcinoma: a nationwide population-based study. PLoS One. 2019;14:e0216828.
- De Giorgi V, Grazzini M, Benemei S, et al. Propranolol for off-label treatment of patients with melanoma: results from a cohort study. JAMA Oncol. 2018;4:e172908.
- Rico M, Baglioni M, Bondarenko M, et al. Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models. Oncotarget. 2017;8:2874-2889.
- Chisholm KM, Chang KW, Truong MT, et al. β-Adrenergic receptor expression in vascular tumors. Mod Pathol. 2012;25:1446-1451.
- Leaute-Labreze C, Dumas de la Roque E, Hubiche T, et al. Propranolol for severe hemangiomas of infancy. N Engl J Med. 2008;358:2649-2651.
- Maddox JC, Evans HL. Angiosarcoma of skin and soft tissue: a study of forty-four cases. Cancer. 1981;48:1907-1921.
- Morgan MB, Swann M, Somach S, et al. Cutaneous angiosarcoma: a case series with prognostic correlation. J Am Acad Dermatol. 2004;50:867-874.
- Zhou S, Liu P, Jiang W, et al. Identification of potential target genes associated with the effect of propranolol on angiosarcoma via microarray analysis. Oncol Lett. 2017;13:4267-4275.
PRACTICE POINTS
- In one classic presentation, cutaneous angiosarcoma characteristically appears as a bruiselike patch on the head and neck of an elderly gentleman.
- Although cutaneous angiosarcoma typically portends a poor prognosis at the time of diagnosis, adjunctive oral propranolol may be a promising and relatively benign therapy, posited to afford benefit in a manner similar to its efficacy in the treatment of infantile hemangiomas.
Use of Dupilumab in Severe, Multifactorial, Chronic Itch for Geriatric Patients
To the Editor:
Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.1 Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.2 Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.3-7
Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (TH2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.
An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.
Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.
Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.
Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.14 We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.
Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.17 Diminishing pruritus is difficult and often aided by management of the underlying renal disease.18
In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.19 Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits TH2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.20 The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.10 The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.
- World’s older population grows dramatically. News release. National Institute on Aging. Published March 28, 2016. Accessed December 23, 2022. http://www.nih.gov/news-events/news-releases/worlds-older-population-grows-dramatically
- Grundmann S, Ständer S. Chronic pruritus: clinics and treatment. Ann Dermatol. 2011;23:1-11.
- Berger TG, Shive M, Harper GM. Pruritus in the older patient: a clinical review. JAMA. 2013;310:2443-2450. doi:10.1001/jama.2013.282023
- Valdes-Rodriguez, R, Mollanazar NK, González-Muro J, et al. Itch prevalence and characteristics in a Hispanic geriatric population: a comprehensive study using a standardized itch questionnaire. Acta Derm Venereol. 2015;95:417-421. doi:10.2340/00015555-1968
- Li J, Tang H, Hu X, et al. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol. 2010;51:106-112.
- Choi EH, Man MQ, Xu P, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol. 2007;127:2847-2856.
- Fenske NA, Lober CW. Structural and functional changes of normal aging skin. J Am Acad Dermatol. 1986;15(4 pt 1):571-585.
- Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140:633-643. doi:10.1016/j.jaci.2017.07.006
- Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;70:3-11.
- Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138:500-508.
- Valdes-Rodriguez R, Stull C, Yosipovitch G. Chronic pruritus in the elderly: pathophysiology, diagnosis and management. Drugs Aging. 2015;32:201-215. doi:10.1007/s40266-015-0246-0
- Misery L, Brenaut E, Le Garrec R, et al. Neuropathic pruritus. Nat Rev Neurol. 2014;10:408-416.
- Yamaoka H, Sasaki H, Yamasaki H, et al. Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy. Diabetes Care. 2010;33:150-155.
- Brenaut E, Marcorelles P, Genestet S, et al. Pruritus: an underrecognized symptom of small-fiber neuropathies. J Am Acad Dermatol. 2015;72:328-332.
- Adigun M, Badu LA, Berner NM, et al. Uremic pruritus review. US Pharm. 2015;40:HS12-HS15.
- Simonsen E, Komenda P, Lerner B, et al. Treatment of uremic pruritus: a systematic review. Am J Kidney Dis. 2017;70:638-655.
- Carstens E, Akiyama T, eds. Itch: Mechanisms and Treatment. CRC Press/Taylor & Francis; 2014.
- Shirazian S, Aina O, Park Y, et al. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017;10:11-26.
- Brummer GC, Wang LT, Sontheimer RD. A possible role for dupilumab (Dupixent) in the management of idiopathic chronic eczematous eruption of aging. Dermatol Online J. 2018;24:13030/qt55z1f6xh.
- Silverberg JI, Brieva J. A successful case of dupilumab treatment for severe uremic pruritus. JAAD Case Rep. 2019;5:339-341.
To the Editor:
Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.1 Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.2 Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.3-7
Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (TH2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.
An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.
Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.
Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.
Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.14 We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.
Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.17 Diminishing pruritus is difficult and often aided by management of the underlying renal disease.18
In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.19 Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits TH2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.20 The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.10 The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.
To the Editor:
Today’s geriatric population is the fastest growing in history. The National Institutes of Health predicts there will be over 1.5 billion individuals aged 65 years and older by the year 2050: 17% of the world’s population.1 Pruritus—either acute or chronic (>6 weeks)—is defined as a sensory perception that leads to an intense desire to scratch.2 Chronic pruritus is an increasing health concern that impacts quality of life within the geriatric population. Elderly patients have various risk factors for developing chronic itch, including aging skin, polypharmacy, and increased systemic comorbidities.3-7
Although the therapeutic armamentarium for chronic itch continues to grow, health care providers often are hesitant to prescribe medications for geriatric patients because of comorbidities and potential drug-drug interactions. Novel biologic therapies now provide alternatives for this complex population. Dupilumab is a fully humanized, monoclonal antibody approved for treatment-resistant atopic dermatitis. This biologic prevents helper T-cell (TH2) signaling, IL-4 and IL-13 release, and subsequent effector cell (eg, mast cell, eosinophil) activity.8-10 The combined efficacy and safety of this medication has changed the treatment landscape of resistant atopic dermatitis. We present the use of dupilumab in a geriatric patient with severe and recalcitrant itch resistant to numerous topical and oral medications.
An 81-year-old man presented to the clinic with a long history of generalized pruritic rash. His medical history was significant for insulin-dependent type 2 diabetes mellitus (T2DM), hypertension, and renal cancer following a right nephrectomy. Laboratory results approximately 14 months prior to the visit revealed a blood urea nitrogen level of 31 mg/dL (reference range, 7–20 mg/dL), creatinine level of 2.20 mg/dL (reference range, 0.7–1.3 mg/dL), and glomerular filtration rate of 29 mL/min (reference range, 90–120 mL/min). Physical examination revealed numerous pink excoriated papules on the face, neck, trunk, and extremities. Lichenified plaques were present on both arms and legs. The patient received the diagnosis of severe atopic dermatitis with greater than 10% body surface area involvement. The investigator global assessment score was 4/4, indicating severe disease burden, and biopsy results reported spongiotic dermatitis. He proceeded to trial various topical corticosteroids, including hydrocortisone ointment 2.5%, betamethasone valerate ointment 0.01%, fluocinonide ointment 0.05%, and mupirocin ointment without benefit. Three subsequent courses of oral steroids failed to provide durable relief. At this point, the peak pruritus numerical rating scale (NRS) score was 7/10, indicating severe pruritus, with a negative impact on the patient’s quality of life and sleep.
Therapy was switched to tacrolimus acetonide ointment 0.1%, betamethasone dipropionate ointment 0.05%, and triamcinolone acetonide ointment 0.1%. Eleven days later, the patient denied experiencing any response to the topical regimen and sought alternative therapy for the itch and associated poor sleep; the NRS score was 10/10, indicating very severe pruritus. Prednisone 20 mg and doxepin 10 mg were initiated for symptom management until the intended transition to dupilumab. The patient began dupilumab with a loading dose of 600 mg, then 300 mg every other week thereafter. At 2- and 4-month follow-up, the patient reported notable relief in symptoms. The rash had improved, and the NRS score decreased from 10/10 to 3/10. He endorsed improved sleep and quality of life.
Pruritus may arise from a series of age-related mechanisms such as structural and chemical changes within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease (CKD).5,6,11 Identifying the underlying etiology often is difficult and involves a complete history and physical examination as well as an appropriate contextualized laboratory workup.
Our patient’s comorbid T2DM and renal disease may have contributed to the pruritus. Type 2 diabetes mellitus can cause diabetic neuropathy, a sequela known to lead to various complications, including pruritus. One study identified a 4-fold increase in pruritus in those with diabetic polyneuropathy compared with age-matched nondiabetics.12,13 An additional study found that pruritus was present in 70% of patients with small fiber neuropathy.14 We needed to consider the role of our patient’s insulin-dependent T2DM and potential underlying neuropathy when addressing the pruritic symptoms.
Furthermore, our patient’s stage IV CKD and elevated urea level also may factor into the pruritus. The pathophysiology of CKD-associated pruritus (also referred to as uremic pruritus) remains poorly understood. Suggested mechanisms include immune-mediated neural inflammation and erroneous nociceptive-receptor activity.15,16 Although uremic pruritus is appreciated primarily in late dialysis-dependent disease, research shows that a notable portion of those with lesser disease, similar to our patient, also experience a significant itch burden.17 Diminishing pruritus is difficult and often aided by management of the underlying renal disease.18
In addition to disease management, symptomatic treatment incorporates the use of emollients, corticosteroids, and antihistamines. Unfortunately, the clinical response in the elderly population to such regimens often is poor.19 Dupilumab is an optimistic therapeutic option for chronic pruritus. By inhibiting the IL-4α receptor found on helper T cells, this biologic inhibits TH2 differentiation and subsequent inflammatory activity. One report identified an optimistic response to dupilumab in the management of uremic pruritus.20 The remarkable improvement and absence of adverse effects in our patient confirmed the utility and safety of dupilumab in complex cases such as elderly patients with multiple comorbidities. Such relief may result from inhibition of proinflammatory cytokine activity as well as decreased afferent spinal cord itch stimuli.10 The positive results from this case cast a favorable outlook on the treatment of chronic itch in the complex geriatric population.
- World’s older population grows dramatically. News release. National Institute on Aging. Published March 28, 2016. Accessed December 23, 2022. http://www.nih.gov/news-events/news-releases/worlds-older-population-grows-dramatically
- Grundmann S, Ständer S. Chronic pruritus: clinics and treatment. Ann Dermatol. 2011;23:1-11.
- Berger TG, Shive M, Harper GM. Pruritus in the older patient: a clinical review. JAMA. 2013;310:2443-2450. doi:10.1001/jama.2013.282023
- Valdes-Rodriguez, R, Mollanazar NK, González-Muro J, et al. Itch prevalence and characteristics in a Hispanic geriatric population: a comprehensive study using a standardized itch questionnaire. Acta Derm Venereol. 2015;95:417-421. doi:10.2340/00015555-1968
- Li J, Tang H, Hu X, et al. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol. 2010;51:106-112.
- Choi EH, Man MQ, Xu P, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol. 2007;127:2847-2856.
- Fenske NA, Lober CW. Structural and functional changes of normal aging skin. J Am Acad Dermatol. 1986;15(4 pt 1):571-585.
- Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140:633-643. doi:10.1016/j.jaci.2017.07.006
- Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;70:3-11.
- Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138:500-508.
- Valdes-Rodriguez R, Stull C, Yosipovitch G. Chronic pruritus in the elderly: pathophysiology, diagnosis and management. Drugs Aging. 2015;32:201-215. doi:10.1007/s40266-015-0246-0
- Misery L, Brenaut E, Le Garrec R, et al. Neuropathic pruritus. Nat Rev Neurol. 2014;10:408-416.
- Yamaoka H, Sasaki H, Yamasaki H, et al. Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy. Diabetes Care. 2010;33:150-155.
- Brenaut E, Marcorelles P, Genestet S, et al. Pruritus: an underrecognized symptom of small-fiber neuropathies. J Am Acad Dermatol. 2015;72:328-332.
- Adigun M, Badu LA, Berner NM, et al. Uremic pruritus review. US Pharm. 2015;40:HS12-HS15.
- Simonsen E, Komenda P, Lerner B, et al. Treatment of uremic pruritus: a systematic review. Am J Kidney Dis. 2017;70:638-655.
- Carstens E, Akiyama T, eds. Itch: Mechanisms and Treatment. CRC Press/Taylor & Francis; 2014.
- Shirazian S, Aina O, Park Y, et al. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017;10:11-26.
- Brummer GC, Wang LT, Sontheimer RD. A possible role for dupilumab (Dupixent) in the management of idiopathic chronic eczematous eruption of aging. Dermatol Online J. 2018;24:13030/qt55z1f6xh.
- Silverberg JI, Brieva J. A successful case of dupilumab treatment for severe uremic pruritus. JAAD Case Rep. 2019;5:339-341.
- World’s older population grows dramatically. News release. National Institute on Aging. Published March 28, 2016. Accessed December 23, 2022. http://www.nih.gov/news-events/news-releases/worlds-older-population-grows-dramatically
- Grundmann S, Ständer S. Chronic pruritus: clinics and treatment. Ann Dermatol. 2011;23:1-11.
- Berger TG, Shive M, Harper GM. Pruritus in the older patient: a clinical review. JAMA. 2013;310:2443-2450. doi:10.1001/jama.2013.282023
- Valdes-Rodriguez, R, Mollanazar NK, González-Muro J, et al. Itch prevalence and characteristics in a Hispanic geriatric population: a comprehensive study using a standardized itch questionnaire. Acta Derm Venereol. 2015;95:417-421. doi:10.2340/00015555-1968
- Li J, Tang H, Hu X, et al. Aquaporin-3 gene and protein expression in sun-protected human skin decreases with skin ageing. Australas J Dermatol. 2010;51:106-112.
- Choi EH, Man MQ, Xu P, et al. Stratum corneum acidification is impaired in moderately aged human and murine skin. J Invest Dermatol. 2007;127:2847-2856.
- Fenske NA, Lober CW. Structural and functional changes of normal aging skin. J Am Acad Dermatol. 1986;15(4 pt 1):571-585.
- Paller AS, Kabashima K, Bieber T. Therapeutic pipeline for atopic dermatitis: end of the drought? J Allergy Clin Immunol. 2017;140:633-643. doi:10.1016/j.jaci.2017.07.006
- Kabashima K. New concept of the pathogenesis of atopic dermatitis: interplay among the barrier, allergy, and pruritus as a trinity. J Dermatol Sci. 2013;70:3-11.
- Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138:500-508.
- Valdes-Rodriguez R, Stull C, Yosipovitch G. Chronic pruritus in the elderly: pathophysiology, diagnosis and management. Drugs Aging. 2015;32:201-215. doi:10.1007/s40266-015-0246-0
- Misery L, Brenaut E, Le Garrec R, et al. Neuropathic pruritus. Nat Rev Neurol. 2014;10:408-416.
- Yamaoka H, Sasaki H, Yamasaki H, et al. Truncal pruritus of unknown origin may be a symptom of diabetic polyneuropathy. Diabetes Care. 2010;33:150-155.
- Brenaut E, Marcorelles P, Genestet S, et al. Pruritus: an underrecognized symptom of small-fiber neuropathies. J Am Acad Dermatol. 2015;72:328-332.
- Adigun M, Badu LA, Berner NM, et al. Uremic pruritus review. US Pharm. 2015;40:HS12-HS15.
- Simonsen E, Komenda P, Lerner B, et al. Treatment of uremic pruritus: a systematic review. Am J Kidney Dis. 2017;70:638-655.
- Carstens E, Akiyama T, eds. Itch: Mechanisms and Treatment. CRC Press/Taylor & Francis; 2014.
- Shirazian S, Aina O, Park Y, et al. Chronic kidney disease-associated pruritus: impact on quality of life and current management challenges. Int J Nephrol Renovasc Dis. 2017;10:11-26.
- Brummer GC, Wang LT, Sontheimer RD. A possible role for dupilumab (Dupixent) in the management of idiopathic chronic eczematous eruption of aging. Dermatol Online J. 2018;24:13030/qt55z1f6xh.
- Silverberg JI, Brieva J. A successful case of dupilumab treatment for severe uremic pruritus. JAAD Case Rep. 2019;5:339-341.
PRACTICE POINTS
- A series of age-related mechanisms within the epidermis, underlying neuropathy, medication side effects, infection, malignancy, thyroid dysregulation, liver disease, and chronic kidney disease may contribute to pruritus in elderly patients.
- Patients with mild kidney disease may still experience a recalcitrant and notable itch burden.
- Dupilumab is efficacious and safe in the management of chronic pruritus, even in complex cases such as elderly patients with multiple comorbidities.
Abortion laws link to state-level mortality
States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.
Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
Mortality increases with number of laws
“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.
Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.
Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.
Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.
Findings were published ahead of print in February’s Obstetrics & Gynecology.
Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.
In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
State abortion laws changed dramatically in the study period
The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.
The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.
Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.
Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
Trigger-law states have strong mortality association
Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.
The existence of trigger laws is likely a proxy for other factors, they write.
“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.
Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.
The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.
“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.
They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.
Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.
One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.
Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
Mortality increases with number of laws
“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.
Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.
Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.
Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.
Findings were published ahead of print in February’s Obstetrics & Gynecology.
Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.
In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
State abortion laws changed dramatically in the study period
The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.
The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.
Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.
Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
Trigger-law states have strong mortality association
Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.
The existence of trigger laws is likely a proxy for other factors, they write.
“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.
Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.
The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.
“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.
They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.
Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.
One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
States that have moderate state abortion laws had lower rates of maternal, fetal, and infant mortality, but not lower all-cause mortality, in reproductive-aged females compared with states that have restrictive laws, new research using 2000-2019 data indicates.
Additionally, having a higher number of laws that restrict abortion in a state was linked with higher maternal and infant mortality in the state, the study states.
Mortality increases with number of laws
“Each additional abortion regulation was associated with an increase in maternal mortality (1.09/100,000 live births; 95% confidence interval, 0.36-1.82) and infant mortality (0.20/1,000 live births; 95% CI, 0.12-0.26),” the authors write.
Lorie M. Harper, MD, MSCI, with the department of women’s health, University of Texas at Austin, led a team that simultaneously studied four categories of mortality: all-cause mortality in females ages 15-49 years; maternal mortality; infant mortality; and fetal mortality.
Her team did a retrospective cohort study using the Centers for Disease Control and Prevention’s WONDER (Wide-ranging ONline Data for Epidemiologic Research) database. WONDER collects publicly available data with information on mortality by state.
Data were available from 2000 to 2019 for all-cause, maternal, and infant mortality. Fetal mortality data were available from 2005 to 2019.
Findings were published ahead of print in February’s Obstetrics & Gynecology.
Though the study was done before the Supreme Court decision overturning Roe v. Wade in June 2022, its findings may shed light on potential trends depending on states’ decisions.
In the wake of the Dobbs v. Jackson Women’s Health Organization, an estimated 33 million U.S. women will live in states without available abortion services, the authors note.
State abortion laws changed dramatically in the study period
The authors chose the 2-decade time frame because data could be accessed for both maternal and infant mortality for all the years and because state level abortion laws changed dramatically in that time.
The Guttmacher Institute has analyzed each state’s abortion policy landscape and scored states as restrictive, moderate, or supportive. Certain types of abortion laws were associated with higher rates of all-cause mortality in reproductive-age females.
Those laws included trigger laws (the laws that automatically outlaw abortion in a state when federal law is overturned), laws that limit access to medication abortion, and parental consent laws, according to the paper.
Additionally, states that restrict access to abortion have higher rates of maternal and infant death, even after accounting for the general health of the population.
Trigger-law states have strong mortality association
Blair G. Darney, PhD, MPH, with the department of obstetrics and gynecology, Oregon Health & Science University and the OHSU-PSU School of Public Health in Portland, and two OHSU coauthors note in an accompanying editorial that having a trigger law in place was associated with elevations in all four mortality measures. However, trigger laws had not yet been enacted during the study.
The existence of trigger laws is likely a proxy for other factors, they write.
“[T]he relationship between trigger laws and increased mortality may more likely be explained by other factors that were not considered in the analysis than by laws that were not enacted at the time of the study,” the editorialists write.
Those factors may include lack of Medicaid expansion, socioeconomic inequities, and other policies.
The editorialists also caution that just because some types of abortion restrictions don’t appear to increase mortality, it doesn’t mean they aren’t harmful.
“For example, laws prohibiting private or Medicaid insurance coverage for abortions were not associated with maternal mortality, but these laws may simply shift the burden of payment to the individual seeking an abortion or be mitigated by funds that support an individual’s out-of-pocket cost for care. The lack of an association may therefore reflect women’s resilience and their ability to obtain needed health care in the face of financial challenges,” they write.
They point out that, conversely, Targeted Regulation of Abortion Providers (TRAP) laws, which supporters say protect women, have been associated instead with increases in maternal mortality.
Dr. Harper and study coauthors, noting that the relationship between abortion laws and mortality is complex, urge states with restrictive abortion laws to consider proven countermeasures to offset the rates, including Medicaid expansion.
One coauthor served on a medical advisory board, was a site primary investigator for several clinical trials, and received royalties from UpToDate for two topics related to trial of labor after cesarean. The other authors did not report any potential conflicts of interest. Dr. Darney’s institution receives research funding from Organon and the Office of Population Affairs on which she is the primary investigator, and she is a member of the board of directors of the Society of Family Planning and a deputy editor at Contraception. She has received an honorarium from ACOG for committee work. The other editorialists did not report any potential conflicts of interest.
FROM OBSTETRICS & GYNECOLOGY
Year in Review: How Targeted Drug Therapies Have Expanded Breast Cancer Treatment Options in 2022
Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC.
The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat.
In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC.
In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.
The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.
The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.
Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC.
The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat.
In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC.
In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.
The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.
The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.
Breast cancer (BC) is the most diagnosed cancer and the second leading cause of cancer deaths in women. In 2022, more than 275,000 women were diagnosed with BC, and at least 43,000 of these cases resulted in death. With targeted drug therapy for treating BC now approved by the US Food and Drug Administration (FDA) and available (or in the late phases of clinical trials and pending availability and FDA approval), clinicians are beginning to be able to move away from a “one-size-fits-all” treatment approach that has been used in the past, enhancing prognosis and survival rates in their patients living with BC.
The new targeted drug therapies available are more precise and individualized. They treat patients more effectively because they are based on the patient’s own biology. These therapies open the possibility of having more valuable treatment options, which can be beneficial for the outcome of many patients diagnosed with BC—especially the highly aggressive forms that were previously difficult to treat.
In March 2022, the FDA approved the drug olaparib to treat HER2-, high-risk, early breast cancer (EBC). The approval was made after the conclusion of the phase 3 OlympiA trial. The clinical trial results showed a statistically significant improvement in overall survival rates (by 32%) with adjuvant olaparib compared with placebo for germline BRCA1/2-mutated EBC.
In August 2022, the FDA approved the antibody drug conjugate fam-trastuzumab deruxtecan-nxki (or T-DXd), which is the first FDA-approved therapy targeted to treat patients who have the HER2-low BC subtype. It is also approved for patients with unresectable or metastatic HER2+ breast cancer who have already been treated with 2 or more prior anti-HER2–based therapies in the metastatic setting. The approval of T-DXd was given on the basis of DESTINY-Breast04, a randomized, multicenter, open-label clinical trial that was published in June 2022. T-DXd had been previously approved in HER2+ metastatic breast cancer.
The results from the phase 3 CAPItello-291 clinical trial of capivasertib in combination with fulvestrant suggests the combination could become a new treatment option for patients with hormone receptor–positive, HER2-low, locally advanced or metastatic BC following recurrence or progression after treatment with endocrine therapy and a CDK4/6 inhibitor. Capivasertib is a novel, selective, ATP-competitive, pan-AKT kinase inhibitor. In clinical trials, the drug was shown to successfully block activity of the cancer-driving protein molecule AKT. This research was presented at the 2022 San Antonio Breast Cancer Symposium, and the findings demonstrated a significant improvement in the overall population, as well as the subgroup of patients with PI3K pathway–altered tumors.
The year 2022 was full of exciting discoveries in the field of targeted drug therapies for treating BC, expanding patients’ treatment options and giving hope to people who have been diagnosed with breast cancer and their loved ones. In addition, emerging technologies such as immunotherapy and new antibody-drug conjugates continue to be evaluated as potential treatment options for treating breast cancer in the near future.
We Have the Tools to Prevent Cervical Cancer— So Why Are Rates Increasing?
Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.
Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.
Cervical cancer screening is often hailed as the most successful screening program ever implemented. Despite these past successes, cervical cancer incidence is no longer decreasing and is actually rising significantly in younger women within the United States. In a country with a well-established screening program, effective screening tools, and HPV vaccination, it seems unfathomable that we are witnessing an increase in cervical cancers. This alarming trend should be cause for concern among all healthcare professionals.