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U.S. finally hits its stride with COVID-19 vaccination rollouts
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Each afternoon, Cyrus Shahpar, MD, the data guru for the White House COVID-19 Response Team, sends an email to staffers with the daily count of COVID-19 vaccinations delivered in the United States.
The numbers, collected from states ahead of the final figures being posted on the Centers for Disease Control and Prevention website, act as a report card of sorts on the team’s efforts.
On Saturday, April 3, it was a new record: 4.1 million vaccinations delivered in a single day, more than the total population of some states.
While the United States has a long way to go before it is done with COVID-19, there’s finally some good news in the nation’s long and blundering slog through the pandemic.
After a rocky start in December 2020 and January 2021, vaccination is happening faster than nearly anyone thought possible. As more people see their friends and family roll up their sleeves, hesitancy is dropping, too.
In settings where large numbers of people are vaccinated, such as nursing homes, COVID-19 cases and deaths have plunged.
Those gains, however, haven’t been shared equally. According to CDC data, 69% of people who are fully vaccinated are White, while just 8% are Black and about 9% are Hispanic, a group that now represents most new COVID-19 cases.
Officials say that’s partly because the vaccines were rolled out to the elderly first. The average life expectancy for Black people in the United States is now age 72, which means there were fewer people of color represented in the first groups to become eligible. Experts are hopeful that underrepresented groups will start to catch up as more states open up vaccinations to younger people.
Based on overall numbers of daily vaccine doses, the United States ranks third, behind China and India. America ranks fourth – behind Israel, the United Kingdom, and Chile – in the total share of the population that’s been vaccinated, according to the website Our World in Data.
A positive development
It’s a stunning turnaround for a country that failed for months to develop effective tests, and still struggles in some quarters to investigate new cases and quarantine their contacts.
The 7-day rolling average of vaccines administered in the United States is currently more than 3 million a day.
“We knew that we needed to get to 3 million a day at some point, if we were going to get most people vaccinated this year, but I don’t think that most people expected it to happen this early,” said Eric Toner, MD, a senior scholar with the Johns Hopkins Center for Health Security in Baltimore.
Before taking office, President Joe Biden pledged to get 100 million shots in arms within his first 100 days in office. After hitting that goal in late March, he doubled it, to 200 million vaccinations by April 30. After first saying all adults should be eligible to get in line for the vaccine by May 1, on April 6, he bumped up that date to April 19.
Some media reports have seen this repeated moving of the goalposts as calculated – an unstated strategy of underpromising and overdelivering with the aim of rebuilding public trust.
But others pointed out that, even if that’s true, the goals being set aren’t easy, and hitting them has never been a given.
“I think the Biden administration really gets a lot of credit for pushing the companies to get more vaccine out faster than they had planned to,” Dr. Toner said. “And the states have really responded as well as the federal government in terms of getting vaccination sites going. So we’re not only getting the vaccines, we’re getting it into people’s arms faster than expected.”
Others agree.
“We’re doing an amazing job, and I think the U.S. is really beginning to bend the curve,” said Carlos del Rio, MD, an infectious disease specialist and distinguished professor of medicine at Emory University, Atlanta.
“I think overall it’s just that everybody’s putting in a ton of work to get it done,” he said.
On April 3, the day the United States hit its vaccination record, he was volunteering to give vaccinations.
“I mean, of all the bad things we do to people as clinicians, this is one thing that people are very happy about, right?” Dr. del Rio said.
He said he vaccinated a young woman who asked if she could video chat with her mom, who was feeling nervous about getting the shot. He answered her mom’s questions, and later that day, she came down to be vaccinated herself.
‘We view it as a war’
The White House COVID-19 Response Team has worked hard to better coordinate the work of so many people at both the federal and state levels, Andy Slavitt, senior adviser for the team, said in an interview.
“We view it as a war, and in a war, you do everything: You bring experienced personnel; you bring all the resources to bear; you create multiple routes,” Mr. Slavitt said. “You don’t leave anything to chance.”
Among the levers the administration has pulled, using the Defense Production Act has helped vaccine manufacturers get needed supplies, Mr. Slavitt said.
The administration has set up an array of Federal Emergency Management Agency–run community vaccination centers and mobile vaccination sites to complement state-led efforts, and it’s activated a federal health law called the Public Readiness and Emergency Preparedness Act, which provides immunity from liability for retired doctors and nurses, among others, who sign up to help give vaccinations. That’s helped get more people into the field giving shots.
The administration also canceled a plan to allocate vaccines to states based on their pace of administration, which would have punished underperforming states. Instead, doses are allocated based on population.
In a media call on April 7, when asked whether the administration would send additional vaccines to Michigan, a state that’s seeing a surge of COVID-19 cases with more transmissible variants, Mr. Slavitt said they weren’t managing vaccine supply “according to some formula.”
He said they were distributing based on population “because that’s fundamental,” but were also locating vaccines “surgically in places that have had the greatest disease and where people have the greatest exposure.”
He said sites like community health centers and retail pharmacies have the power to order vaccines directly from the federal government, which helps get more supply to harder-hit areas.
Mr. Slavitt said hitting 4.1 million daily vaccinations on April 3 was gratifying.
“I’ve seen photographs ... of people breaking down in tears when they get their vaccine, people who are giving standing ovations to active military for taking care of them,” he said, “and I think about people who have gone for a long time without hope, or who have been very scared.
“It’s incredibly encouraging to think about maybe a few million people taking a step back to normal life again,” he said.
A version of this article first appeared on Medscape.com.
Enzymatic injections show durable improvement in buttock cellulite
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
follow-up in an ongoing, 5-year, phase 3b, open-label extension study, Michael H. Gold, MD, said at Innovations in Dermatology: Virtual Spring Conference 2021.
However, outcomes in that study, as well as in the earlier pivotal trials, were assessed via physician and patient subjective assessments of aesthetic appearance. In a separate presentation at the conference, Michael S. Kaminer, MD, presented a different study evaluating the objective quantifiable effects of CCH on buttock cellulite dimple volume using three-dimensional imaging. The results, indicating that smaller cellulite dimples responded better than larger dimples, he noted, were unexpected.
Discussant Zoe D. Draelos, MD, who practices in High Point, N.C., and is a consulting professor of dermatology at Duke University, Durham, N.C., put the two studies in perspective, explaining that there are multiple challenges associated with the use of CCH to treat buttock cellulite, and dermatologists need to understand them in order to maximize the benefit.
“There’s definitely a market for this therapy,” she observed, noting the plethora of over-the-counter products and devices sold for removal of cellulite. “I think if you manage patient expectations, this will be a very, very successful procedure.”
In 2020, the Food and Drug Administration approved subcutaneous injections of CCH (marketed under the brand name QWO) for treatment of cellulite in women’s buttocks on the basis of the randomized RELEASE-1 and -2 trials. But while this is a new indication for CCH, it is not a new drug. The medication has been approved for years for treatment of fibrotic band contracture disorders, namely Dupuytren’s contracture and Peyronie’s disease. The mechanism of action for treatment of cellulite involves a process dubbed enzymatic subcision, in which CCH breaks down mature collagen and stimulates new collagen formation and fat redistribution in an effort to achieve smoother skin contour.
“This adds a whole new wrinkle to injectables available in dermatology. We have fillers, we have toxins, and now we have enzymatic subcision,” Dr. Draelos commented.
Durability of effects
Dr. Gold, founder of the Gold Skin Care Center and at the Tennessee Clinical Research Center, Nashville, reported on 483 women with moderate to severe buttock cellulitis who completed the 71-day, randomized, double-blind, phase 3 RELEASE-1 or RELEASE-2 studies and then enrolled in the open-label extension study. At the end of the randomized trial, 61.7% of women experienced at least a 1-level improvement on the Patient-Reported Photonumeric Cellulite Severity Scale (PR-PCSS), compared with 36.7% of placebo controls. The key finding in the interim analysis of the extension study: After the first 6 months, during which no one received any additional therapy, 52.7% of the CCH group still had at least a 1-level improvement in PR-PCSS, compared with the randomized trial baseline, as did 32.6% of controls.
Similarly, 63% of CCH-treated patients showed at least a 1-level improvement in the Clinician-Reported Photonumeric Cellulite Severity Scale (CR-PCSS) from baseline to the end of the randomized trial, and 52.7% met that standard after 6 months off treatment in the open-label extension. In contrast, the control group had response rates of 36.7% and 32.6%. There were no long-term safety concerns, according to Dr. Gold.
Measuring cellulite dimple volume shrinkage
Dr. Kaminer and coinvestigators measured the change in cellulite dimple volume from baseline to 30 days after the final injection of 33 buttock dimples in 27 women in order to get a quantifiable sense of the effectiveness of the CCH injection. To their surprise, smaller-volume dimples up to 118 mm3 showed a mean 43% reduction in volume, a significantly better result than the 15.8% reduction seen in dimples greater than 118 mm3.
“That’s almost counterintuitive, right? You’d think that larger dimples would have a bigger improvement, but it turns out that the smaller dimples do better,” he said at the conference sponsored by MedscapeLIVE! and the producers of the Hawaii Dermatology Seminar and Caribbean Dermatology Symposium.
Also, cellulite dimples in women age 40 and under responded significantly better than those in older women, added Dr. Kaminer, a dermatologist in private practice in Chestnut Hill, Mass., who is also on the faculty at Yale University, New Haven, Conn., and Brown University, Providence, R.I.
Challenges in using CCH therapy
Dr. Draelos, who is familiar with CCH, having worked on some earlier studies of the product, commented that “this is really the first medical treatment for cellulite that’s been proven to work.”
That being said, there are challenges with this therapy. While roughly 53% of women rated themselves as having at least a 1-level improvement after 6 months of follow-up, so did 33% of placebo-treated controls, for a placebo-subtracted 20% response.
“Is a 1-grade improvement going to be enough for women to engage in this procedure? You do need to remember that it takes multiple injections: most need at least three injections to see durable impact. And there’s discomfort during the procedure and afterwards during the healing process because the mechanism of action is enzymatic. You’re breaking down fibrous bands, and that’s a proinflammatory process. Many women who undergo this procedure may have discomfort and bruising, and they should be warned that this is not a procedure to do before taking a cruise or wearing a bikini. Also, it’s important to note that many women will have discomfort in the area where they sit, so if they have a job where they need to be sitting for long periods of time they need to plan their activities around this particular procedure,” the dermatologist said.
Another consideration: “The area they actually studied – the buttocks – is an area where I’m not sure a lot of women would expose their skin in public. I think thigh dimpling is more bothersome because it shows in shorts and other types of clothing. We need to figure out if the injections work on the posterior thighs, the most common place most postpubertal women get cellulite,” Dr. Draelos noted.
She wasn’t surprised that smaller cellulite dimples did better. Larger dimples presumably have a broader fibrous attachment and tighter fibrous band. She found the less robust outcomes in women over age 40 similarly unsurprising, since cellulitis seems to worsen with age. Cellulitis can’t really be called a disease, anyway, since it occurs in about 90% of postpubertal women.
One last tip about managing patient expectations: “Let a woman know that it’ll be better, but it won’t be gone,” she said.
Dr. Gold and Dr. Kaminer reported serving as paid investigators for and consultants to Endo Pharmaceuticals, the study sponsor and manufacturer of CCH, as well as for several other pharmaceutical companies.
MedscapeLIVE! and this news organization are owned by the same parent company.
FROM INNOVATIONS IN DERMATOLOGY
Arkansas first state to ban transgender medical treatments for youths
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Arkansas has become the first state to pass a law prohibiting doctors from giving gender-affirming medical treatments to transgender youths, CNN reported.
Gov. Asa Hutchinson had vetoed the bill on April 5, calling it a “product of the cultural war in America.” But on April 6, the state House and Senate voted to override the veto, making it state law, CNN reported.
At least 17 other states are considering similar legislation, but the Arkansas bill was the first to reach the governor’s desk, the Washington Post reported.
The bill bans doctors from prescribing puberty blockers, hormone therapies, or genital-altering surgeries for anybody under 18. Ever referring a youth for such treatment from another doctor is prohibited.
“It is of grave concern to the General Assembly that the medical community is allowing individuals who experience distress at identifying with their biological sex to be subjects of irreversible and drastic nongenital gender reassignment surgery and irreversible, permanently sterilizing genital gender reassignment surgery, despite the lack of studies showing that the benefits of such extreme interventions outweigh the risks,” the text of the bill said.
Gov. Hutchinson, a Republican, had called the measure a “vast government overreach” in announcing his veto.
“The bill is overbroad, extreme, and does not grandfather those young people who are currently under hormone treatment,” Gov. Hutchinson said. “The young people who are currently under a doctor’s care will be without treatment when this law goes into effect. That means they will be looking to the black market or go out of state ... to find the treatment that they want and need. This is not the right path to put them on.”
Many medical groups have come out against this kind of legislation. The American Academy of Child and Adolescent Psychiatry says it “strongly opposes any efforts – legal, legislative, and otherwise – to block access to these recognized interventions.”
Chase Strangio, the deputy director for transgender justice with the American Civil Liberty Union’s LGBTQ & HIV Project, complimented Gov. Hutchinson for his veto. On April 6, he said the ACLU is preparing to challenge the bill in court, CNN said.
A version of this article first appeared on Medscape.com.
Contradictions abound in ‘The End of Mental Illness’
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Daniel G. Amen, MD, is an American psychiatrist well-known for his eponymous clinics, television appearances, and series of books on mental health. One of his latest books, “The End of Mental Illness,” summarizes many of his views on the causes of and treatments for mental illnesses.
Dr. Amen’s approaches – such as his advocacy for the widespread use of single photon emission computed tomography (SPECT) imaging – are somewhat controversial and at times fall outside the mainstream of current psychiatric thought. So does “The End of Mental Illness” contain anything of value to the average practicing psychiatrist? (It should be noted that I listened to this as an audiobook and took notes as I listened. This does limit my ability to directly quote portions of the text, but I believe my notes are reliable.)
He begins the book by pointing out that the term “mental illness” might be better replaced with the term “brain illness.” With this shift in terminology, Dr. Amen introduces a theme that recurs throughout the book: That mental illnesses ultimately stem from various ways in which the brain can be harmed. While the suggested change in terminology might help reduce the stigma associated with psychiatric illnesses, Dr. Amen is surprisingly timid about implementing this term in his own book. He repeatedly refers to “brain health/mental health” issues instead of discarding the “mental” term altogether. Even his BRIGHT MINDS acronym for risk factors for mental illnesses includes the term “mind” instead of “brain.”
Continuing the theme of challenging terminology, Dr. Amen goes on to decry the weaknesses of the DSM system of nosology. This is a valid point, because under the current system, the same patient may receive differing diagnoses depending on which provider is seen and how certain symptoms are interpreted. Yet, here again, Dr. Amen does not seem to adhere to his own advice: He uses DSM terminology throughout the book, speaking of depression, anxiety, bipolar disorder, and ADHD. An oddity (which, admittedly, could have been the audiobook reader’s mistake rather than an error in the original text) is that the DSM is referred to as the “Diagnostic and Structural Manual” rather than the Diagnostic and Statistical Manual. He criticizes the DSM for its imprecision, pointing out the variety of symptom combinations that can produce the same diagnoses and how similar symptoms may overlap between differing diagnoses. Yet, his descriptions of common SPECT patterns (his preferred tool to assist in diagnosis) make it clear that here, too, there is a lot of overlap. As an example, ADHD was associated with at least three of the imaging patterns he described. It is also somewhat ironic how Dr. Amen obliquely criticizes the American Psychiatric Association for profiting from the use of the DSM, when SPECT imaging is expensive and profits his own organization.
Dr. Amen repeatedly asserts that psychiatry is unique among medical specialties for making diagnoses based on symptom clusters rather than direct visualization of the affected organ. Yet, psychiatry is not, in fact, unique in making diagnoses in this way. Some examples of diagnoses based on symptom clusters from other medical specialties are systemic lupus erythematosus, fibromyalgia, and chronic fatigue syndrome. Although he asserts that SPECT imaging better demonstrates the root cause of mental illnesses, it is unclear from his book whether this is actually the case.
The descriptions for the ways in which Dr. Amen uses SPECT (which, admittedly, are vague and presumably simplified for a general audience) suggest that he has made observations correlating specific imaging patterns with certain emotional/behavioral outcomes. However, the imaging patterns he describes in the book can be interpreted to represent multiple different mental conditions, making it clear that SPECT is not a laserlike diagnostic tool that produces a single, indisputable diagnosis. Accuracy with SPECT seems especially questionable in light of two case examples he shares where brain imaging was interpreted as representing illness, but the patients were not demonstrating any signs of mental dysfunction. In one case, Dr. Amen opined that the patient’s vibrant spiritual life “overrode” the sick brain, but if this is true,
Patient testimonials are provided, asserting that SPECT imaging helped them know “exactly” what treatment would help them. One cannot help but wonder whether part of the benefit of SPECT imaging is a placebo effect, boosting the confidence of patients that the treatment they are receiving is personalized and scientifically sound. A similar trend is currently seen more broadly in psychiatry with the widespread promotion of pharmacogenetic testing. Such testing may bolster patient confidence in their medication, but its value in improving patient outcomes has not been established.1
Dr. Amen outlines a brief history of mental health care, including differing approaches and therapies from the time of Sigmund Freud up to the present. His outline is somewhat critical of the perceived shortcomings of his psychiatric forebears, yet this seems entirely unnecessary. All scientific disciplines must start somewhere and build from limited knowledge to greater. Is it necessary to belittle Freud for not being able to do SPECT imaging in the 1800s?
Interestingly, Dr. Amen leaves cognitive-behavioral therapy (CBT), a landmark, evidence-based form of psychotherapy, out of his overview of the history of psychiatry. He does go on to mention CBT as part of the treatment offerings of the Amen Clinics, which could leave the lay reader with the incorrect impression that CBT is a treatment unique to Amen Clinics. Similarly, at one point Dr. Amen writes about “what I call automatic negative thoughts.” This phrasing could confuse readers who might not know that automatic thoughts are a concept endemic to CBT.
Dr. Amen writes repeatedly about the Amen Clinics 4 Circles, four key areas of life that can contribute to mental health. These areas are biological, psychological, social, and spiritual. While Amen Clinics may have come up with the term “4 Circles,” the biopsychosocial model of understanding illness was developed by George Engel, MD, in 1977, and current discussions of this model frequently incorporate a spiritual dimension as well.2
Dr. Amen’s writing at times mischaracterizes psychotropic medications in unhelpful ways. He speaks of psychotropic medications generally as being addictive. While this is certainly true for stimulants and benzodiazepines, most would agree that this does not apply to many other commonly used medications in psychiatry, including selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, antipsychotics, and mood stabilizers. He also paints with a broad brush when he states that anxiety medications can cause dementia. A concerning link has been demonstrated between benzodiazepine use and dementia,3 but SSRIs (which are considered first-line medications for anxiety) are not known to cause dementia and may actually delay progression from mild cognitive impairment to Alzheimer’s dementia.4 His mention of medication use affecting a patient’s insurability could have the unfortunate effect of scaring away suffering individuals from seeking help. The one category of psychiatric medication he does not seem concerned about is psychostimulants, which is odd – given the addictive, cardiovascular, and other risks associated with that medication class.
In contrast to his skepticism regarding many psychotropic medications, Dr. Amen expresses significant enthusiasm regarding nutraceutical use. While there has been research in this area supporting a role for some nutraceutical interventions, there is still a need for more rigorous studies.5 To support his endorsement of natural remedies, Dr. Amen mentions that Hippocrates recommended herbs and spices for many health conditions. But Hippocrates lived more than 2,000 years ago, and the state of medicine has advanced significantly since then.
Dr. Amen also mentions that 80% of the developing world relies upon natural or herbal remedies as the primary source of medicine. While he frames this statement as supporting his endorsement of such remedies, it could conversely be said that this is evidence of the need to make pharmacological interventions more widely available in the developing world.
Much of “The End of Mental Illness” is dedicated to reviewing specific risk factors that could cause harm to a person’s mental well-being. One example is head trauma. Dr. Amen documents at least one instance in which he was convinced that his patient had experienced head trauma, and questioned the patient again and again about possible brain injuries. One must wonder whether the positive results of such focused, repetitive questioning might be evidence of confirmation bias, as a search to confirm the preexisting belief of head trauma could lead to overlooking alternative explanations for a patient’s symptoms.
Another risk factor dwelt upon is exposure to toxins. One toxin Dr. Amen rightly recommends avoiding is tobacco smoke. Yet, his approach to advocate for a tobacco-free lifestyle is somewhat problematic. He lists chemicals contained in tobacco smoke, and then names unpleasant items that share those ingredients, such as paint. This smacks of the same sloppy logic manifested in social media memes decrying the use of vaccines by listing their ingredients alongside scary-sounding products that contain identical ingredients (for example, vaccines contain formaldehyde, which is used to embalm dead bodies!). This is analogous to saying that water is bad for you because it contains hydrogen, which is also an ingredient in atomic bombs.
Dr. Amen makes the blanket recommendation to avoid products containing “chemicals.” This is a difficult recommendation to interpret, since literally all matter is made of chemicals. It seems that Dr. Amen is leaning into the vague idea of a “chemical” as something artificially created in a lab, which must, therefore, be dangerous.
Along these lines, Dr. Amen suggests that if a person doesn’t know what is in a specific food item, it should not be eaten. Although this sounds reasonable on the surface, if people were told the names of the proteins and chemical compounds that make up many naturally occurring plants or meats, they would likely not recognize many of them. Dr. Amen dedicates space to list seemingly benign exposures – such as eating nonorganic produce, using two or more beauty products each day, or touching grocery store receipts – as possible “toxins.” By contrast, there is a certain irony in the absence of any mention of the risks associated with radiation from the SPECT imaging he staunchly advocates for. One potential risk of the book listing so many “toxins” to avoid is that patients could waste valuable time and energy eliminating exposures that pose little or no risk, rather than focusing efforts on well-established treatments.
In light of the observations and critiques offered above, one might come away with the impression that I would not recommend “The End of Mental Illness.” However, although one can nitpick details in the book, some of its bigger ideas make it worth commending to readers. Dr. Amen rightfully emphasizes the need for psychiatrists and patients to think more broadly about mental health issues beyond the use of pills. He justifiably criticizes the “15-minute med check” model of practice and the idea that medications are the end-all, be-all of treatment. He demonstrates an appropriate appreciation for the serious risks of reliance on benzodiazepines.6 Dr. Amen points out important contributions from Viktor Frankl, MD, to the field of psychiatry, which may go overlooked today. He also helpfully points out that bipolar disorder may often be misdiagnosed (although he attributes the misdiagnosis to traumatic brain injury, whereas other psychiatrists might say the misdiagnosis is due to borderline personality disorder).
Much of what Dr. Amen writes is sensible, and psychiatrists would do well to adopt the following steps he advocates for: Taking a comprehensive biopsychosocial-spiritual approach to the assessment and treatment of patients; thinking broadly in their differential diagnoses and not forgetting their medical training; understanding that medication alone is often not sufficient to make lasting, positive change in a person’s life; paying attention to healthy habits such as diet, exercise, sleep, and social activity; and knowing that CBT is a valuable tool that can change lives.
There is much to appreciate in “The End of Mental Illness,” especially the overarching idea that psychiatry isn’t just a symptom checklist and a prescription pad. Rather, achieving mental well-being often requires broader thinking and sustained lifestyle changes.
Although I did not agree with everything in the book, it did cause me to think and reflect on my own practice. I read “The End of Mental Illness” with colleagues in my department, and it stimulated a lively discussion. Isn’t that ultimately what a psychiatrist would want from a book like this – the opportunity to reflect, discuss, and potentially improve one’s own practice?
Dr. Weber is physician lead in the department of psychiatry at Intermountain Healthcare Budge Clinic, Logan (Utah) Psychiatry. He disclosed no relevant financial relationships.
References
1. JAMA Netw Open. 2020;3(12). doi: 10.1001/jamanetworkopen.2020.27909.
2. Curr Opin Psychiatry. 2014;27:358-63.
3. BMJ 2014. doi: 10.1136/bmj.g5205.
4. Am J Psychiatry. 2018 Mar 1;175:232-41.
5. Am J Psychiatry. 2016 Jun 1;173:575-87.
6. Current Psychiatry. 2018 Feb;17(2):22-7.
Everyday chemicals are linked to declines in human fertility
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Chemicals that pervade our modern world – plastics, pesticides, stain repellents, components of personal hygiene products – are contributing to a decades-long decline in fertility and could pose health risks even into future generations, according to an explosive new book by Shanna Swan, PhD, an environmental and reproductive epidemiologist at the Icahn School of Medicine at Mount Sinai, New York.
Dr. Swan laid out the case that endocrine-disrupting chemicals (EDCs) such as phthalates and bisphenol A (BPA) threaten human existence, a conclusion that stems in part from her 2017 meta-analysis that showed a 52% drop in sperm counts from 1973 to 2011 in men in North America, Europe, and Australia.
“This alarming rate of decline could mean the human race will be unable to reproduce itself if the trend continues,” Dr. Swan said in her book, “Count Down: How Our Modern World Is Threatening Sperm Counts, Altering Male and Female Reproductive Development, and Imperiling the Future of the Human Race,” (New York: Scribner, 2021) coauthored with health journalist Stacey Colino.
Her premise that EDCs pose a risk to both male and female fertility is underscored by new research. A March 2021 article in Human Reproduction links prenatal chemical exposures to lowered fertility in a study of 1,045 Swiss military conscripts.
The Swiss men, aged 18-22 years, were significantly more likely to have low semen volume and low total sperm count if their mothers reported that they had occupational exposures to four or more endocrine-disrupting chemicals while they were pregnant. These EDCs, which mimic natural hormones, included pesticides, heavy metals, phthalates, alkylphenolic compounds, and solvents that can be found in agricultural work or hair and beauty salons.
These chemicals are not so-called “forever chemicals” that persist in the human body. But the Swiss study still showed an association between exposure during pregnancy and the future fertility of the male children. “Those apparently small exposures that pass quickly can affect development,” said Dr. Swan, who was not affiliated with the research. “It takes very little in terms of time and amount of chemicals to alter fetal development.”
Health risks beyond reproduction
While Count Down is placing a new spotlight on chemical hazards, some major medical organizations have already taken positions on the risks. “Reducing exposure to toxic environmental agents is a critical area of intervention for ob.gyns.,” the American College of Obstetricians and Gynecologists said in an environmental policy priority. “The Endocrine Society is concerned that human health is at risk because the current extensive scientific knowledge on EDCs and their health effects is not effectively translated to regulatory policies that fully protect populations from EDC exposures.”
But for the medical community, addressing the impact of EDCs goes beyond advocacy for regulatory and legislative changes, Dr. Swan said in an interview. Physicians should talk to patients about the importance of reducing their chemical exposure to safeguard their overall health.
“Reproductive health and particularly sperm count, subfertility, and infertility are predictors of lifelong health,” she said. That includes associations between reproductive disorders and “the risk of heart disease, obesity, reproductive cancers and, perhaps most dramatically, with a shortened lifespan.”
Some medical schools are including information on environmental health and exposure risks in the curriculum, said Tracey Woodruff, PhD, MPH, director of the program on reproductive health and the environment at the University of California, San Francisco. She urged physicians to ask patients about potential occupational exposures to hazardous chemicals and provide information about ways to reduce everyday exposures.
For example, safer options include buying organic produce, microwaving food in glass rather than plastic containers and avoiding products that contain phthalate or BPA. “If you’re going to talk to people about what they eat, that’s a perfect venue for talking about the environment,” said Dr. Woodruff, who coedited the textbook, Environmental Impacts on Reproductive Health and Fertility (Cambridge University Press: Cambridge, England, 2010).
The UCSF program provides patient guides in English and Spanish with suggestions of ways to reduce chemical exposures at work and at home.
Limits in the data
Michael Eisenberg, MD, a urologist and director of male reproductive medicine and surgery at Stanford (Calif.) University Medical Center, often gets questions from patients about how lifestyle and environmental exposures affect male fertility. (In her book, Dr. Swan also discusses how factors such as diet, exercise, smoking, and stress can affect male and female fertility.)
He found the evidence convincing that certain chemicals impact fertility – although, of course, it isn’t ethically possible to do randomized, controlled trials in which some people are intentionally exposed to chemicals to measure the effects. Along with adopting other healthy habits, he advised patients to avoid chemical exposures.
“It’s reasonable to try to eat organic and be mindful of where some of these exposures come from and try to minimize them to the extent possible,” he said.
Rebecca Sokol, MD, MPH, an endocrinologist and expert in male reproductive health, demonstrated the toxic effects of lead on sperm production in studies conducted on rats. But she views low-dose chemical exposure from everyday products as just one aspect of modern reproductive risks, some of which have stronger associations. For example, testosterone therapy impairs sperm production, and finasteride (a medication for male pattern baldness) has been linked to a reversible decline in sperm count.
“When it comes to these ubiquitous chemicals like phthalate and BPA, we explain to the patient that maybe they’re harmful, but we can’t say for sure,” because of the lack of causal data, said Dr. Sokol, professor emerita at the University of Southern California, who was on the panel that drafted the American Urological Association and American Society of Reproductive Medicine guideline on the diagnosis and treatment of male infertility.
Nonetheless, she advised patients to try to reduce exposures. “I don’t see us eradicating all the chemicals that might be bad for us unless we go back to another era. But we can do the best we can to avoid what we can.”
A call to action
Dr. Swan likened awareness of the health threat of chemical exposures to the gradual recognition of the climate crisis as a global imperative. Yet in some ways, the scientific work on chemical effects is even more daunting. The Environmental Protection Agency lists more than 86,000 chemicals on its inventory of chemical substances manufactured or imported into the United States.
Little is known about the potential effects of many chemicals that we inhale, ingest or absorb through our skin, Dr. Swan said. In her book, she noted the impact on wildlife – for example, reproductive abnormalities in frogs, alligators, and birds that were exposed to EDCs.
Yet Dr. Swan also takes solace in the lessons from the animal kingdom. Decades after the pesticide DDT, a neurotoxin and endocrine-disruptor, was banned in the United States in 1972, the bald eagle has made a comeback from near-extinction. She also pointed to a 2018 study which found that, while mice exposed to bisphenols passed on reproductive effects to offspring, when the exposures stopped, the effects disappeared after several generations.
“If we stop poisoning ourselves, we can turn this around,” said Dr. Swan. “That’s what I want people to know.”
Count Down frames the issues in language that is much starker than typically found in academic publications. But that is what’s necessary to draw attention to the effects of chemical exposures on human health and reproduction, Dr. Swan said. “I’m saying this in fairly extreme terms to alarm people, to make them realize it is a crisis and they have to act.”
No disclosures were reported.
Implementation of a Pharmacist-Managed Transitions of Care Tool
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
Effective transitions of care (TOC) are essential to ensure quality continuity of care after hospital discharge. About 20 to 30% of patients experience an adverse event (AE) in the peridischarge period when discharged to the community.1 Additionally, about two-thirds of AEs are preventable.1 The Joint Commission has identified various breakdowns in care that are associated with poor outcomes, including a lack of standardized discharge procedures, limited time dedicated to discharge planning and processes, and patients who lack the necessary resources or skills to implement discharge care plans.2
Background
The most impactful TOC programs are those that target patients who are at high risk for readmission or adverse outcomes.3 Factors such as advanced age, polypharmacy, cognitive impairment, and lack of social support are patient characteristics that have been associated with unfavorable outcomes after discharge.4 To identify this subset of high-risk individuals, various risk assessment scores have been developed, ranging from those that are used locally at the facility level to those that are nationally validated. The LACE score (Length of hospital stay; Acuity of the admission; Comorbidities measured with the Charlson comorbidity index score; and Emergency department visits within the past 6 months) is a validated index scoring tool that is used to identify medical and surgical patients at risk for readmission or death within 30 days of hospital discharge. On a 19-point scale, a score of ≥ 10 is considered high risk.5 Specific to the US Department of Veterans Affairs (VA), the Care Assessment Needs (CAN) score was developed to risk stratify the veteran population. The CAN score is generated using information including patient demographics, medical conditions, VA health care utilization, vital signs, laboratory values, medications, and socioeconomic status. This score is expressed as a percentile that compares the probability of death or admission among veterans at 90 days and 1 year postdischarge. Veterans in the 99th percentile have a 74% risk for these adverse outcomes at 1 year.6
The Joint Commission states that a fundamental component to assuring safe and effective TOC is medication management, which includes the involvement of pharmacists.2 TOC programs with pharmacist involvement have shown significant improvements related to reduced 30-day hospital readmissions and health care costs in addition to significant medication-related interventions.7-9 While this body of evidence continues to grow and demonstrates that pharmacists are an integral component of the TOC process, there is no gold standard program. Brantley and colleagues noted that a weakness of many TOC programs is that they are one dimensional, meaning that they focus on only 1 element of care transitions or 1 specific patient population or disease.10
There is well-supported evidence of high-impact interventions for pharmacists involved early in the admission process, but data are less robust on the discharge process. 11,12 Therefore, the primary focus of this project was to develop a pharmacist-based TOC program and implement a process for communicating high-risk patients who are discharging from our hospital across the continuum of care.
Setting
The Richard L. Roudebush VA Medical Center (RLRVAMC) is a tertiary care referral center for veterans in Indiana and eastern Illinois. Acute care clinical pharmacists are fully integrated into the acute care teams and practice under a comprehensive care model. Pharmacists attend daily patient care rounds and conduct discharge medication reconciliation for all patients with additional bedside counseling for patients who are being discharged home.
Primary care services are provided by patient aligned care teams (PACTs), multidisciplinary teams composed of physicians, advanced practice nurses, pharmacists, mental health care providers, registered nurses, dieticians, and care coordinators. Ambulatory Care or PACT clinical pharmacists are established within each RLRVAMC PACT clinic and provide comprehensive care management through an independent scope of practice for several chronic diseases, including hypertension, type 2 diabetes mellitus (T2DM), dyslipidemia, hypothyroidism, and tobacco cessation. Prior to this project implementation, there was no formalized or standardized method for facilitating routine communication of patients between acute care and PACT pharmacists in the TOC process.
Pilot Study
In 2017, RLRVAMC implemented a TOC pharmacy program pilot. A pharmacy resident and both acute care and PACT clinical pharmacy specialists (CPSs) developed the service. The pilot program was conducted from September 1, 2017 to March 1, 2018. The initial phase consisted of the development of an electronic TOC tool to standardize communication between acute care and PACT pharmacists. The TOC tool was created on a secure site accessible only to pharmacy personnel and not part of the formal medical record. (Figure 1).
The acute care pharmacist identified high-risk patients through calculated CAN and LACE scores during the discharge process and offered PACT pharmacist follow-up to the patient during bedside discharge counseling. Information was then entered into the TOC tool, including patient identifiers and a message with specific information outlining the reason for referral. PACT pharmacists routinely reviewed the tool and attempted to phone each patient within 7 days of discharge. Follow-up included medication reconciliation and chronic disease management as warranted at the discretion of the PACT pharmacist. All postdischarge follow-up appointments were created and documented in the electronic health record. A retrospective chart review was completed on patients who were entered into the TOC tool.
Patients were eligible for referral if they were discharged during the study period with primary care established in one of the facility’s PACT clinics. Additionally, patients had to meet ≥ 1 of the following criteria, deeming them a high risk for readmission: LACE score ≥ 10, CAN score ≥ 90th percentile, or be considered high risk based on the discretion of the acute care pharmacist. Patients were included in the analysis if they met the CAN or LACE score requirement. Patients were excluded if they received primary care from a site other than a RLRVAMC PACT clinic. This included non-VA primary care, home-based primary care, or VA community-based outpatient clinics (CBOCs). Patients also were excluded if they required further institutional care postdischarge (ie, subacute rehabilitation, extended care facility, etc), discharged to hospice, or against medical advice.
The average referral rate per month during the pilot study was 19 patients, with 113 total referrals during the 6-month study period. Lower rates of index emergency department (ED) visits (5.3% vs 23.3%) and readmissions (1% vs 6.7%) were seen in the group of patients who received PACT pharmacist follow-up postdischarge compared with those who did not. Additionally, PACT pharmacists were able to make > 120 interventions, averaging 1.7 interventions per patient. Of note, these results were not statistically analyzed and were assessed as observational data to determine whether the program had the potential to be impactful. The results of the pilot study demonstrated positive outcomes associated with having a pharmacist-based TOC process and led to the desire for further development and implementation of the TOC program at the RLRVAMC. These positive results prompted a second phase project to address barriers, make improvements, and ensure sustainability.
Methods
Phase 2 was a quality improvement initiative; therefore, institutional review board approval was not needed. The aim of phase 2 was to improve, expand, and sustain the TOC program that was implemented in the pilot study. Barriers identified after discussion with acute care and PACT pharmacists included difficulty in making referrals due to required entry of cumbersome readmission risk factor calculations, limiting inclusion to patients who receive primary care at the main hospital facility, and the expansion of pharmacy staff with new pharmacists who were not knowledgeable of the referral process.
Design
To overcome barriers, 4 main targeted interventions were needed: streamlining the referral process, enhancing pharmacy staff education, updating the discharge note template, and expanding the criteria to include patients who receive care at VA CBOCs. The referral process was streamlined by removing required calculated readmission risk scores, allowing pharmacist judgement to take precedence for referrals. Focused face-to-face education was provided to acute care and PACT pharmacists about the referral process and inclusion criteria to increase awareness and provide guidance of who may benefit from entry into the tool. Unlike the first phase of the study, education was provided for outpatient staff pharmacists responsible for discharging patients on the weekends. Additionally, the pharmacists received a printed quick reference guide of the information covered during the education sessions (Figure 2). Referral prompts were embedded into the standard pharmacy discharge note template to serve as a reminder to discharging pharmacists to assess patients for inclusion into the tool and provided a direct link to the tool. Expansion to include VA CBOCs occurred postpilot study, allowing increased patient access to this TOC service. All other aspects of the program were continued from the pilot phase.
Patients were eligible if they were discharged from RLRVAMC between October 1, 2018 and February 28, 2019. Additionally, the patient had to be established in a PACT clinic for primary care and have been referred to the tool based on the discretion of an acute care pharmacist. Patients were excluded if they were discharged against medical advice or to any facility where the patient and/or caregiver would not be responsible for medication administration (eg, subacute rehabilitation, extended care facility), or if the patient refused pharmacy follow-up.
Outcomes
The primary outcomes assessed were all-cause and index ED visits and readmissions within 30 days of discharge. All-cause ED visits and readmissions were defined as a second visit to RLRVAMC , regardless of readmission diagnosis. Index ED visits and readmissions were defined as those that were related to the initial admission diagnosis. Additional data collected and analyzed included the number of patients referred by pharmacists, number and type of medication discrepancies, medication changes, counseling interventions, time to follow-up postdischarge, and number of patients added to the PACT pharmacist’s clinic schedule for further management. A discrepancy identified by a PACT pharmacist was defined as a difference between the discharge medication list and the patient-reported medication list at the time of follow-up. Patients who were referred to the TOC tool but were unable to be reached by telephone served as the control group for this study.
Data Collection
A retrospective chart review was completed on patients entered into the tool. Data were collected and kept in a secured Microsoft Excel workbook. Baseline characteristics were analyzed using either a χ2 for nominal data or Student t test for continuous data. The primary outcomes were analyzed using a χ2 test. All statistical tests were analyzed using MiniTab 19 Statistical Software.
Results
Pharmacists added 172 patients into the TOC tool; 139 patients met inclusion criteria. Of those excluded, most were because the PACT pharmacist did not attempt to contact the patient since they already had a primary care visit scheduled postdischarge (Table 1). Of the 139 patients who met the inclusion criteria, 99 were successfully contacted by a PACT pharmacist. Most patients were aged in their 60s, male, and white. Both groups had a similar quantity of outpatient medications on admission and medication changes made at discharge. Additionally, both groups had a similar number of patients with hospitalizations and/or ED visits in the 3 months before hospital admission that resulted in TOC tool referral (Table 2).
Hospital Readmission
Hospital 30-day readmission rates for patients who were successfully followed by pharmacy compared with those who were not were 5.1% vs 15.0% (P = .049) for index readmissions and 8.1% vs 27.5% (P = .03) for all-cause readmissions. No statistically significant difference existed between those patients with follow-up compared with those without follow-up for either index (10.1% vs 12.5%, respectively; P = .68) or for all-cause ED visit rates (15.2% vs 20.0%, respectively; P = .49).
Patient Encounters
The average time to follow-up was 8.8 days, which was above the predetermined goal of contact within 7 days. Additionally, this was a decline from the initial pilot study, which had an average time to reach of 4.7 days. All patients reached by a pharmacist received medication reconciliation, with ≥ 28% of patients having ≥ 1 discrepancy. There were 43 discrepancies among all patients. Of the discrepancies, 25 were reported as errors performed by the patient, and 18 were from an error during the discharge process. The discrepancies that resulted from patient error were primarily patients who took the wrong dose of prescribed medications. Other patient discrepancies included taking medications not as scheduled, omitting medications (both intentionally and mistakenly), continuing to take medications that had been discontinued by a health care provider and improper administration technique. Examples of provider errors that occurred during the discharge process included not ordering medications for patient to pick up at discharge, not discontinuing a medication from the patient’s profile, and failure to renew expired prescriptions.
Additional counseling was provided to 75% of patients: The most common reason for counseling was T2DM, hypertension, and dyslipidemia management. PACT pharmacists changed medication regimens for 27.3% of patients for improved control of chronic diseases or relief of medication AEs.
At the end of each visit, patients were assessed to determine whether they could benefit from additional pharmacy follow-up. Thirty-seven patients were added to the pharmacist schedules for disease management appointments. The most common conditions for these appointments were T2DM, hypertension, tobacco cessation, and hyperlipidemia. Among the 37 patients who had pharmacy follow-up, there were 137 additional pharmacy appointments within the study period.
Program Referrals
After expansion to include the VA CBOCs, elimination of the elevated LACE or CAN score requirement, and additional staff education, the rate of referrals per month increased during phase 2 in comparison to the pilot study (Figure 3). There were a mean (SD) of 34 (10) referrals per month. Although not statistically analyzed, it is an objective increase in comparison to a mean 19 referrals per month in the pilot study.
Discussion
The continued development and use of a pharmacist-driven TOC tool at RLRVAMC increased communication and follow-up of high-risk patients, demonstrated the ability of pharmacists to identify and intervene in medication-related issues postdischarge, and successfully reduce 30-day readmissions. This program emphasized pharmacist involvement during the discharge process and created a standardized mechanism for TOC follow-up, addressing multiple areas that were identified by The Joint Commission as being associated with poor outcomes. The advanced pharmacy practice model at RLRVAMC allowed for a multidimensional program, including prospective patient identification and multiple pharmacy touchpoints. This is unique in comparison to many of the one-dimensional programs described in the literature.
Polypharmacy has been identified as a major predictor of medication discrepancies postdischarge, and patients with ≥ 10 active medications have been found to be at highest risk.13,14 Patients in this study had a mean 13 active medications on admission, with a mean 5 medication changes at discharge. PACT pharmacists documented 28 of 99 patients with ≥ 1 medication-related discrepancy at postdischarge reconciliation. This 28% discrepancy rate is consistent with discrepancy rates previously reported in the literature, which ranged from 14 to 45% in large meta-analyses.14,15 The majority of these discrepancies (58%) were related to patients who took the wrong dose of a prescribed medication.
Targeted interventions to overcome barriers in the pilot study increased the referral rates to the TOC tool; however, the increase in referral rate was associated with increased time to follow up by ambulatory care pharmacists. The extended follow-up times were seen most often in the 2 busiest primary care clinics, one of which is considered a teaching clinic for medical residents. Pharmacists were required to integrate these calls into their normal work schedule and were not provided additional time for calling, allowing for an increased follow-up time. The increased follow-up time likely contributed to the increased number of patients excluded due to already having PACT follow-up, giving more time for the primary care provider to have an appointment with the patient. The ambulatory care pharmacist could then determine whether further intervention was needed. In the summer of 2018, a decrease in referral rates occurred for a short time, but this is likely explained by incoming new residents and staff within the pharmacy department and decreased awareness among the new staff. The enhanced staff education took place during September 2018 and lead to increased referral rates compared with those seen in months prior.
PACT pharmacists were not only able to identify discrepancies, but also provide timely intervention on a multitude of medication-related issues by using their scope of practice (SOP). Most interventions were related to medication or disease counseling, including lifestyle, device, and disease education. The independent SOP of our PACT pharmacists is a unique aspect of this program and allowed pharmacists to independently adjust many aspects of a patient’s medication regimen during follow-up visits.
The outcomes of 30-day index and all-cause readmissions, as well as index and all-cause ED visit rates, were lower in the subset of patients who received PACT pharmacist follow-up after discharge (Table 3). The difference was most pronounced in the all-cause readmission rates: Only 8.1% of patients who received PACT follow-up experienced a readmission compared with 27.5% of those who did not. The difference between the groups regarding ED visit rates were not as pronounced, but this may be attributed to a limited sample size. These data indicate that the role of the pharmacist in identifying discrepancies and performing interventions at follow-up may play a clinically significant part in reducing both ED visit rates and hospital readmissions.
Limitations
There are some limitations identified within this study. Although the referral criteria were relaxed from the pilot study and enhanced education was created, continued education regarding appropriate referral of TOC patients continues to be necessary given intermittent staff changeover, incorporation of pharmacy trainees, and modifications to clinic workflow. Patients who were discharged to facilities were not included. This ensured that appropriate and consistent PACT pharmacist follow-up would be available, but likely reduced our sample size.
Although performing this study in a closed health care system with pharmacists who have independent SOPs is a strength of our study, also it can limit generalizability. Not all facilities house both acute care and ambulatory care in one location with wide SOPs to allow for comprehensive and continued care. Last, this study used convenience sampling, potentially introducing selection bias, as patients unable to be reached by PACT pharmacists may inherently be at increased risk for hospital readmission. However, in the 3 months preceding the hospital admission that resulted in TOC tool referral, both groups had a similar number of patients with hospital admissions and ED visits.
The TOC tool has become fully integrated into the daily workflow for both acute care and PACT pharmacists. After the conclusion of the study period, the referral rates into the tool have been maintained at a steady level, even surpassing the rates seen during the study period. In comparison with the pilot study, PACT pharmacists reported a subjective increase in referrals placed for procedures such as medication reconciliation or adherence checks. This is likely because acute care pharmacists were able to use their clinical judgement rather than to rely solely on calculated readmission risk scores for TOC tool referral.
The success of the TOC program led to the expansion to other specialty areas. ED pharmacists now refer patients from the ED who were not admitted to the hospital but would benefit from PACT follow-up. Additionally, the option to refer hematology and oncology patients was added to allow these patients to be followed up by our hematology/oncology CPSs by phone appointments. Unique reasons for follow-up for this patient population include concerns about delayed chemotherapy cycles or chemotherapy-associated AEs.
Conclusions
This study outlines the creation and continued improvement of a pharmacist-based TOC program. The program was designed as a method of communication between acute care and PACT pharmacists about high-risk patients. The creation of this program allowed PACT pharmacists not only to identify discrepancies and make interventions on high-risk patients, but also demonstrate that having pharmacists involved in these programs may have a positive impact on readmissions and ED visits. The success of the TOC tool at the RLRVAMC has led to its expansion and is now an integral part of the daily workflow for both acute care and PACT pharmacists.
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
1. Forster AJ, Murff HJ, Peterson JF, Gandhi TK, Bates DW. The incidence and severity of adverse effects affecting patients after discharge from the hospital. Ann Intern Med. 2003;138(3):161-167. doi:10.7326/0003-4819-138-3-200302040-00007
2. The Joint Commission. Transitions of care: the need for collaboration across entire care continuum. Published February 2013. Accessed February 25, 2021. http://www.jointcommission.org/assets/1/6/TOC_Hot_Topics.pdf
3. Leppin AL, Gionfriddo MR, Kessler M, et al. Preventing 30-day hospital readmissions: a systematic review and meta-analysis of randomized trials. JAMA Intern Med. 2014;174(7):1095-1107. doi:10.1001/jamainternmed.2014.1608
4. Medicare Hospital Compare. Readmissions and deaths. Accessed February 25, 2021. https://www.cms.gov/Medicare/Quality-Initiatives-Patient-Assessment-Instruments/HospitalQualityInits/VA-Data
5. van Walraven C, Dhalla IA, Bell C, et al. Derivation and validation of an index to predict early death or unplanned readmission after discharge from hospital to the community. CMAJ. 2010;182(6):551-557. doi:10.1503/cmaj.091117
6. US Department of Veteran Affairs. Care Assessment Needs (CAN) score report. Updated May 14, 2019. Accessed February 25, 2021. https://www.va.gov/HEALTHCAREEXCELLENCE/about/organization/examples/care-assessment-needs.asp
7. Schnipper JL, Kirwin JL, Cotugno MC, et al. Role of pharmacist counseling in preventing adverse drug events after hospitalization. Arch Intern Med. 2006;166(5):565-571. doi:10.1001/archinte.166.5.565
8. Phatak A, Prusi R, Ward B, et al. Impact of pharmacist involvement in the transitional care of high-risk patients through medication reconciliation, medication education, and post-discharge call-backs. J Hosp Med. 2016;11(1):40-44. doi:10.1002/jhm.2493
9. Coleman EA, Min SJ, Chomiak A, Kramer AM. Posthospital care transitions: patterns, complications, and risk identification. Health Serv Res. 2004;39(5):1449-1465. doi:10.1111/j.1475-6773.2004.00298.x
10. Brantley AF, Rossi DM, Barnes-Warren S, Francisco JC, Schatten I, Dave V. Bridging gaps in care: implementation of a pharmacist-led transitions of care program. Am J Health Syst Pharm. 2018;75(5)(suppl 1):S1-S5. doi:10.2146/ajhp160652
11. Scarsi KK, Fotis MA, Noskin GA. Pharmacist participation in medical rounds reduces medical errors. Am J Health Syst Pharm. 2002;59(21):2089-2092. doi:10.1093/ajhp/59.21.2089
12. Pevnick JM, Nguyen C, Jackevicius CA, et al. Improving admission medication reconciliation with pharmacists or pharmacy technicians in the emergency department: a randomised controlled trial. BMJ Qual Saf. 2018;27:512-520. doi:10.1136/bmjqs-2017-006761.
13. Kirwin J, Canales AE, Bentley ML, et al; American College of Clinical Pharmacy. Process indicators of quality clinical pharmacy services during transitions of care. Pharmacotherapy. 2012;32(11):e338-e347. doi:10.1002/phar.1214
14. Kwan JL, Lo L, Sampson M, et al. Medication reconciliation during transitions of care as a patient safety strategy: a systematic review. Ann Intern Med. 2013;158(5, part 2):397-403. doi:10.7326/0003-4819-158-5-201303051-00006
15. Stitt DM, Elliot DP, Thompson SN. Medication discrepancies identified at time of hospital discharge in a geriatric population. Am J Geriatr Pharmacother. 2011;9(4):234-240. doi:10.1016/j.amjopharm.2011.06.002
What’s the future of telehealth? It’s ‘complicated’
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
pre-AAD meeting.
“We have seen large numbers of children struggle with access to school and access to health care because of lack of access to devices, challenges of broadband Internet access, culture, language, and educational barriers – just having trouble being comfortable with this technology,” said Natalie Pageler, MD, a pediatric intensivist and chief medical information officer at Stanford Children’s Health, Palo Alto, Calif.
“There are also privacy concerns, especially in situations where there are multiple families within a household. Finally, it’s important to remember that policy and reimbursement issues may have a significant effect on some of the socioeconomic barriers,” she added. “For example, many of our families who don’t have access to audio and video may be able to do a telephone call, but it’s important that telephone calls be considered a form of telehealth and be reimbursed to help increase the access to health care by these families. It also makes it easier to facilitate coordination of care. All of this leads to decreased time and costs for patients, families, and providers.”
Within the first few weeks of the pandemic, Dr. Pageler and colleagues at Stanford Children’s Health observed an increase from about 20 telehealth visits per day to more than 700 per day, which has held stable. While the benefits of telehealth are clear, many perceived barriers exist. In a study conducted prior to the COVID-19 pandemic, researchers identified a wide variety of barriers to implementation of telehealth, led by reimbursement, followed by poor business model sustainability, lack of provider time, and provider interest.
“Some of the barriers, like patient preferences for inpatient care, lack of provider interest in telehealth, and lack of provider time were easily overcome during the COVID pandemic,” Dr. Pageler said. “We dedicated the time to train immediately, because the need was so great.”
In 2018, Patrick McMahon, MD, and colleagues at Children’s Hospital of Philadelphia, launched a teledermatology program that provided direct-to-patient “E-visits” and recently pivoted to using this service only for acne patients through a program called “Acne Express.” The out-of-pocket cost to patients is $50 per consult and nearly 1,500 cases have been completed since 2018, which has saved patients and their parents an estimated 65,000 miles driving to the clinic.
“In the last year we have piloted something called “E-Consults,” which is a provider-to-provider, store-and-forward service,” said Dr. McMahon, a pediatric dermatologist and director of teledermatology at CHOP. “That service is not currently reimbursable, but it’s funded through our hospital. We also have live video visits between provider and patient. That is reimbursable. We have done about 7,500 of those.”
In a 2020 unpublished membership survey of SPD members, Dr. McMahon and colleagues posed the question, “How has teledermatology positively impacted your practice over the past year?” The top three responses were that teledermatology was safe during COVID-19, it provided easy access for follow-up, and it was convenient. In response to the question, “What is the most fundamental change needed for successful delivery of pediatric teledermatology?” the top three responses were reimbursement, improved technology, and regulatory changes.
“When we asked about struggles and difficulties, a lot of responses surrounded the lack of connectivity, both from a technological standpoint and also that lack of connectivity we would feel in person – a lack of rapport,” Dr. McMahon said. “There’s also the inability for us to touch and feel when we examine, and we worry about misdiagnosing. There are also concerns about disparities and for us being sedentary – sitting in one place staring at a screen.”
To optimize the teledermatology experience, he suggested four pillars: educate, optimize, reach out, and tailor. “I think we need to draw upon some of the digital education we already have, including a handout for patients [on the SPD website] that offers tips on taking a clear photograph on their smartphones,” he said. “We’re also trying to use some of the cases and learnings from our teledermatology experiences to teach the providers. We are setting up CME modules that are sort of a flashcard-based teaching mechanism.”
To optimize teledermatology experiences, he continued, tracking demographics, diagnoses, number of cases, and turnaround time is helpful. “We can then track who’s coming in to see us at follow-up after a new visit through telehealth,” Dr. McMahon said. “This helps us repurpose things, pivot as needed, and find any glitches. Surveying the families is also critical. Finally, we need clinical support to tee-up visits and to ensure photos are submitted and efficient, and to match diagnoses and family preference with the right modality.”
Another panelist, Justin M. Ko, MD, MBA, who chairs the American Academy of Dermatology’s Task Force on Augmented Intelligence, said that digitally enabled and artificial intelligence (AI)-augmented care delivery offers a “unique opportunity” for increasing access and increasing the value of care delivered to patients.
“The role that we play as clinicians is central, and I think we can make significant strides by doing two things,” said Dr. Ko, chief of medical dermatology for Stanford (Calif.) Health Care. “One: extending the reach of our expertise, and the second: scaling the impact of the care we deliver by clinician-driven, patient-centered, digitally-enabled, AI-augmented care delivery innovation. This opportunity for digital care transformation is more than just a transition from in-person visits to video visits. We have to look at this as an opportunity to leverage the unique aspects of digital capabilities and fundamentally reimagine how we deliver care.”
The AAD’s Position Statement on Augmented Intelligence was published in 2019.
Between March and June of 2021, Neil S. Prose, MD, conducted about 300 televisits with patients. “I had a few spectacular visits where, for example, a teenage patient who had been challenging showed me all of her artwork and we became instantly more connected,” said Dr. Prose, professor of dermatology, pediatrics, and global health at Duke University, Durham, N.C. “Then there’s the potential for a long-term improvement in health care for some patients.”
But there were also downsides to the process, he said, including dropped connections, poor picture and sound quality, patient no-shows, and patients reporting they were unable to schedule a telemedicine visit. “The problems I was experiencing were not just between me and my patients; the problems are systemic, and they have to do with various factors: the portal, the equipment, Internet access, and inadequate or no health insurance,” said Dr. Prose, past president of the SPD.
Portal-related challenges include a lack of focus on culture, literacy, and numeracy, “and these worsen inequities,” he said. “Another issue related to portal design has to do with language. Very few of the portals allow patients to participate in Spanish. This has been particularly difficult for those of us who use Epic. The next issue has to deal with the devices the patients are using. Cell phone visits can be very problematic. Unfortunately, lower-income Americans have a lower level of technology adoption, and many are relying on smartphones for their Internet access. That’s the root of some of our problems.”
To achieve digital health equity, Dr. Prose emphasized the need for federal mandates for tools for digital health access usable by underserved populations and federal policies that increase broadband access and view it as a human right. He also underscored the importance of federal policies that ensure continuation of adequate telemedicine reimbursement beyond the pandemic and urged health institutions to invest in portals that address the needs of the underserved.
“What is the future of telemedicine? The answer is complicated,” said Dr. Prose, who recommended a recently published article in JAMA on digital health equity. “There have been several rumblings of large insurers who plan to pull the rug on telemedicine as soon as the pandemic is more or less over. So, all of our projections about this being a wonderful trend for the future may be for naught if the insurers don’t step up to the table.”
None of the presenters reported having financial disclosures.
FROM THE SPD PRE-AAD MEETING
Gastrointestinal Symptoms and Lactic Acidosis in a Chronic Marijuana User
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
A 57-year-old woman with a history of traumatic brain injury, posttraumatic stress disorder, depression, migraines, hypothyroidism, and a hiatal hernia repair presented to the emergency department with a 1-day history of nausea, vomiting, and diffuse abdominal pain. She reported that her symptoms were relieved by hot showers. She also reported having similar symptoms and a previous gastric-emptying study that showed a slow-emptying stomach. Her history also consisted of frequent cannabis use for mood and appetite stimulation along with eliminating meat and fish from her diet, an increase in consumption of simple carbohydrates in the past year, and no alcohol use. Her medications included topiramate 100 mg and clonidine 0.3 mg nightly for migraines; levothyroxine 200 mcg daily for hypothyroidism; tizanidine 4 mg twice a day for muscle spasm; famotidine 40 mg twice a day as needed for gastric reflux; and bupropion 50 mg daily, citalopram 20 mg daily, and lamotrigine 25 mg nightly for mood.
The patient’s physical examination was notable for bradycardia (43 beats/min) and epigastric tenderness. Admission laboratory results were notable for an elevated lactic acid level of 4.8 (normal range, 0.50-2.20) mmol/L and a leukocytosis count of 10.8×109 cells/L. Serum alcohol level and blood cultures were negative. Liver function test, hemoglobin A1c, and lipase test were unremarkable. Her electrocardiogram showed an unchanged right bundle branch block. Chest X-ray, computed tomography (CT) of her abdomen/pelvis and echocardiogram were unremarkable.
What is your diagnosis?
How would you treat this patient?
This patient was diagnosed with gastrointestinal beriberi. Because of her dietary changes, lactic acidosis, and bradycardia, thiamine deficiency was suspected after ruling out other possibilities on the differential diagnosis (Table). The patient’s symptoms resolved after administration of high-dose IV thiamine 500 mg 3 times daily for 4 days. Her white blood cell count and lactic acid level normalized. Unfortunately, thiamine levels were not obtained for the patient before treatment was initiated. After administration of IV thiamine, her plasma thiamine level was > 1,200 (normal range, 8-30) nmol/L.
Her differential diagnosis included infectious etiology. Given her leukocytosis and lactic acidosis, vancomycin and piperacillin/tazobactam were started on admission. One day later, her leukocytosis count doubled to 20.7×109 cells/L. However, after 48 hours of negative blood cultures, antibiotics were discontinued.
Small bowel obstruction was suspected due to the patient’s history of abdominal surgery but was ruled out with CT imaging. Similarly, pancreatitis was ruled out based on negative CT imaging and the patient’s normal lipase level. Gastroparesis also was considered because of the patient’s history of hypothyroidism, tobacco use, and her prior gastric-emptying study. The patient was treated for gastroparesis with a course of metoclopramide and erythromycin without improvement in symptoms. Additionally, gastroparesis would not explain the patient’s leukocytosis.
Cannabinoid hyperemesis syndrome (CHS) was suspected because the patient’s symptoms improved with cannabis discontinuation and hot showers.1 In chronic users, however, tetrahydrocannabinol levels have a half-life of 5 to 13 days.2 Although lactic acidosis and leukocytosis have been previously reported with cannabis use, it is unlikely that the patient would have such significant improvement within the first 4 days after discontinuation.1,3,4 Although the patient had many psychiatric comorbidities with previous hospitalizations describing concern for somatization disorder, her leukocytosis and elevated lactic acid levels were suggestive of an organic rather than a psychiatric etiology of her symptoms.
Discussion
Gastrointestinal beriberi has been reported in chronic cannabis users who present with nausea, vomiting, epigastric pain, leukocytosis, and lactic acidosis; all these symptoms rapidly improve after thiamine administration.5,6 The patient’s dietary change also eliminated her intake of vitamin B12, which compounded her condition. Thiamine deficiency produces lactic acidosis by disrupting pyruvate metabolism.7 Bradycardia also can be a sign of thiamine deficiency, although the patient’s use of clonidine for migraines is a confounder.8
Chronically ill patients are prone to nutritional deficiencies, including deficiencies of thiamine.7,9 Many patients with chronic illnesses also use cannabis to ameliorate physical and neuropsychiatric symptoms.2 Recent reports suggest cannabis users are prone to gastrointestinal beriberi and Wernicke encephalopathy.5,10 Treating gastrointestinal symptoms in these patients can be challenging to diagnose because gastrointestinal beriberi and CHS share many clinical manifestations.
The patient’s presentation is likely multifactorial resulting from the combination of gastrointestinal beriberi and CHS. However, thiamine deficiency seems to play the dominant role.
There is no standard treatment regimen for thiamine deficiency with neurologic deficits, and patients only retain about 10 to 15% of intramuscular (IM) injections of cyanocobalamin.11,12 The British Committee for Standards in Haematology recommends IM injections of 1,000 mcg of cyanocobalamin 3 times a week for 2 weeks and then reassess the need for continued treatment.13 The British Columbia guidelines also recommend IM injections of 1,000 mcg daily for 1 to 5 days before transitioning to oral repletion.14 European Neurology guidelines for the treatment of Wernicke encephalopathy recommend IV cyanocobalamin 200 mg 3 times daily.15 Low-level evidence with observational studies informs these decisions and is why there is variation.
The patient’s serum lactate and leukocytosis normalized 1 day after the administration of thiamine. Thiamine deficiency classically causes Wernicke encephalopathy and wet beriberi.16 The patient did not present with Wernicke encephalopathy’s triad: ophthalmoplegia, ataxia, or confusion. She also was euvolemic without signs or symptoms of wet beriberi.
Conclusions
Thiamine deficiency is principally a clinical diagnosis. Thiamine laboratory testing may not be readily available in all medical centers, and confirming a diagnosis of thiamine deficiency should not delay treatment when thiamine deficiency is suspected. This patient’s thiamine levels resulted a week after collection. The administration of thiamine before sampling also can alter the result as it did in this case. Additionally, laboratories may offer whole blood and serum testing. Whole blood testing is more accurate because most bioactive thiamine is found in red blood cells.17
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
1. Price SL, Fisher C, Kumar R, Hilgerson A. Cannabinoid hyperemesis syndrome as the underlying cause of intractable nausea and vomiting. J Am Osteopath Assoc. 2011;111(3):166-169. doi:10.7556/jaoa.2011.111.3.166
2. Sharma P, Murthy P, Bharath MM. Chemistry, metabolism, and toxicology of cannabis: clinical implications. Iran J Psychiatry. 2012;7(4):149-156.
3. Antill T, Jakkoju A, Dieguez J, Laskhmiprasad L. Lactic acidosis: a rare manifestation of synthetic marijuana intoxication. J La State Med Soc. 2015;167(3):155.
4. Sullivan S. Cannabinoid hyperemesis. Can J Gastroenterol. 2010;24(5):284-285. doi:10.1155/2010/481940
5. Duca J, Lum CJ, Lo AM. Elevated lactate secondary to gastrointestinal beriberi. J Gen Intern Med. 2016;31(1):133-136. doi:10.1007/s11606-015-3326-2
6. Prakash S. Gastrointestinal beriberi: a forme fruste of Wernicke’s encephalopathy? BMJ Case Rep. 2018;bcr2018224841. doi:10.1136/bcr-2018-224841
7. Friedenberg AS, Brandoff DE, Schiffman FJ. Type B lactic acidosis as a severe metabolic complication in lymphoma and leukemia: a case series from a single institution and literature review. Medicine (Baltimore). 2007;86(4):225-232. doi:10.1097/MD.0b013e318125759a
8. Liang CC. Bradycardia in thiamin deficiency and the role of glyoxylate. J Nutrition Sci Vitaminology. 1977;23(1):1-6. doi:10.3177/jnsv.23.1
9. Attaluri P, Castillo A, Edriss H, Nugent K. Thiamine deficiency: an important consideration in critically ill patients. Am J Med Sci. 2018;356(4):382-390. doi:10.1016/j.amjms.2018.06.015
10. Chaudhari A, Li ZY, Long A, Afshinnik A. Heavy cannabis use associated with Wernicke’s encephalopathy. Cureus. 2019;11(7):e5109. doi:10.7759/cureus.5109
11. Stabler SP. Vitamin B12 deficiency. N Engl J Med. 2013;368(2):149-160. doi:10.1056/NEJMcp1113996
12. Green R, Allen LH, Bjørke-Monsen A-L, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3(1):17040. doi:10.1038/nrdp.2017.40
13. Devalia V, Hamilton MS, Molloy AM. Guidelines for the diagnosis and treatment of cobalamin and folate disorders. Br J Haematol. 2014;166(4):496-513. doi:10.1111/bjh.12959
14. British Columbia Ministry of Health; Guidelines and Protocols and Advisory Committee. Guidelines and protocols cobalamin (vitamin B12) deficiency–investigation & management. Effective January 1, 2012. Revised May 1, 2013. Accessed March 10, 2021. https://www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/vitamin-b12
15. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, Leone MA. EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy. Eur J Neurol. 2010;17(12):1408-1418. doi:10.1111/j.1468-1331.2010.03153.x
16. Wiley KD, Gupta M. Vitamin B1 thiamine deficiency (beriberi). In: StatPearls. StatPearls Publishing LLC; 2019.
17. Jenco J, Krcmova LK, Solichova D, Solich P. Recent trends in determination of thiamine and its derivatives in clinical practice. J Chromatogra A. 2017;1510:1-12. doi:10.1016/j.chroma.2017.06.048
The Natural History of a Patient With COVID-19 Pneumonia and Silent Hypoxemia
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
In less than a year, COVID-19 has infected nearly 100 million people worldwide and caused more than 2 million deaths and counting. Although the infection fatality rate is estimated to be 1% and the case fatality rate between 2% and 3%, COVID-19 has had a disproportionate effect on the older population and those with comorbidities. Some of these findings are mirrored in the US Department of Veterans Affairs (VA) population, which has seen a higher case fatality rate.1-4
As a respiratory tract infection, the most dreaded presentation is severe pneumonia with acute hypoxemia, which may rapidly deteriorate to acute respiratory distress syndrome (ARDS) and respiratory failure.5-7 This possibility has led to early intubation strategies aimed at preempting this rapid deterioration and minimizing viral exposure to health care workers. Intubation rates have varied widely with extremes of 6 to 88%.8,9
However, this early intubation strategy has waned as some of the rationale behind its endorsement has been called into question. Early intubation bypasses alternatives to intubation; high-flow nasal cannula oxygen, noninvasive ventilation, and awake proning are all effective maneuvers in the appropriate patient.10,11 The use of first-line high-flow nasal cannula oxygen and noninvasive ventilation has been widely reported. Reports of first-line use of high-flow nasal cannula oxygen has not demonstrated inferior outcomes, nor has the timing of intubation, suggesting a significant portion of patients could benefit from a trial of therapy and eventually avoid intubation.11-14 Other therapies, such as systemic corticosteroids, confer a mortality benefit in those patients with COVID-19 who require oxygen or mechanical ventilation, but their impact on the progression of respiratory failure and need for intubation are undetermined.
There also are reports of patients who report no signs of respiratory distress or dyspnea with their COVID-19 pneumonia despite profound hypoxemia or high oxygen requirements. Various terms, including silent hypoxemia or happy hypoxia, are descriptive of the demeanor of these patients, and treatment has invariably included oxygen.15,16 Nevertheless, low oxygen measurements have generally prompted higher levels of supplemental oxygen or more invasive therapies.
Treatment rendered may obscure the trajectory of response, which is important to understand to better position options for invasive therapies and other therapeutics. We recently encountered a patient with a course of illness that represented the natural history of COVID-19 pneumonia with low oxygen levels (referred to as hypoxemia for consistency) that highlighted several issues of management.
Case Presentation
A 62-year-old undomiciled woman with morbid obesity, prediabetes mellitus, long-standing schizophrenia, and bipolar disorder presented to our facility for evaluation of dry cough and need for tuberculosis clearance for admittance to a shelter. She appeared comfortable and was afebrile with blood pressure 111/74 mm Hg, heart rate 82 beats per minute. Her respiratory rate was 18 breaths per minute, but the pulse oximetry showed oxygen saturation of 70 to 75% on room air at rest. A chest X-ray showed bibasilar infiltrates (Figure 1), and a rapid COVID-19 nasopharyngeal polymerase chain reaction (PCR) test returned positive, confirmed by a second PCR test. Baseline inflammatory markers were elevated (Figure 2). In addition, the serum interleukin-6 also was elevated to 66.1 pg/mL (normal < 5.0), erythrocyte sedimentation rate elevated to 69 mm/h, but serum procalcitonin was essentially normal (0.22 ng/mL; normal < 20 ng/mL) as was the serum lactate (1.4 mmol/L).
The patient was admitted to the intensive care unit (ICU) for close monitoring in anticipation of the possibility of decompensation based on her age, hypoxia, and elevated inflammatory markers.17 Besides a subsequent low-grade fever (100.4 oF) and lymphopenia (manual count 550/uL), she remained clinically unchanged. Throughout her hospitalization, she maintained a persistent psychotic delusion that she did not have COVID-19, refusing all medical interventions, including a peripheral IV line and supplemental oxygen for the entire duration. Extensive efforts to identify family or a surrogate decision maker were unsuccessful. After consultation with Psychiatry, Bio-Ethics, and hospital leadership, the patient was deemed to lack decision-making capacity regarding treatment or disposition and was placed on a psychiatric hold. However, since any interventions against her will would require sedation, IV access, and potentially increase the risk of nosocomial COVID-19 transmission, she was allowed to remain untreated and was closely monitored for symptoms of worsening respiratory failure.
Over the next 2 weeks, her hypoxemia, inflammatory markers, and the infiltrates on imaging resolved (Figure 2). The lowest daily awake room air pulse oximetry readings are reported, initially with consistent readings in the low 80% range, but on day 12, readings were > 90% and remained > 90% for the remainder of her hospitalization. Therefore, shortly after hospital day 12, she was clinically stable for discharge from acute care to a subacute facility, but this required documentation of the clearance of her viral infection. She refused to undergo a subsequent nasopharyngeal swab but allowed an oropharyngeal COVID-19 PCR swab, which was negative. She remained stable and unchanged for the remainder of her hospitalization, awaiting identification of a receiving facility and was able to be discharged to transitional housing on day 38.
Discussion
The initial reports of COVID-19 pneumonia focused on ARDS and respiratory failure requiring mechanical ventilation with less emphasis on those with lower severity of illness. This was heightened by health care systems that were overwhelmed with large number of patients while faced with limited supplies and equipment. Given the risk to patients and providers of crash intubations, some recommended early intubation strategies.3 However, the natural history of COVID-19 pneumonia and the threshold for intubation of these patients remain poorly defined despite the creation of prognostic tools.17 This patient’s persistent hypoxemia and elevated inflammatory markers certainly met markers of disease associated with a high risk of progression.
The greatest concern would have been her level of hypoxemia. Acceptable thresholds of hypoxemia vary, but general consensus would classify pulse oximetry < 90% as hypoxemia and a threshold for administering supplemental oxygen. It is important to recognize how pulse oximetry readings translate to partial pressure of oxygen (PaO2) measurements (Table 1). Pulse oximetry readings of 90% corresponds to a PaO2 readings of 60 mm Hg in ideal conditions without the influence of acidosis, PaCO2, or temperature. While lower readings are of concern, these do not represent absolute indications for assisted ventilatory support as lower levels are well tolerated in a variety of conditions. A common example are patients with chronic obstructive pulmonary disease. Long-term mortality benefits of continuous supplemental oxygen are well established in specific populations, but the threshold for correction in the acute setting remains a case-by-case decision. This decision is complex and is based on more than an absolute number or the amount of oxygen required to achieve a threshold level of oxygenation.
The PaO2/FIO2 (fraction of inspired oxygen) is a common measure used to address severity of disease and oxygen requirements. It also has been used to define the severity of ARDS, but the ratio is based on intubated and mechanically ventilated patients and may not translate well to those not on assisted ventilation. Treatment with supplemental oxygen also involves entrained air with associated imprecision in oxygen delivery.18 For this discussion, the patient’s admission PaO2/FIO2 on room air would have been between 190 and 260. Coupled with the bilateral infiltrates on imaging, there was justified concern for progression to severe ARDS. Her presentation would have met most of the epidemiologic criteria used in initial case finding for severe COVID-19 cases, including a blood oxygen saturation ≤ 93%, PaO2/FIO2 < 300 with infiltrates involving close to if not exceeding 50% of the lung.
With COVID-19 pneumonia, the pathologic injury to the alveoli resembles that of any viral pneumonia with recruitment of predominantly lymphocytic inflammatory cells that fill the alveoli, derangements in ventilation/perfusion mismatch as the core mechanism of hypoxemia with interstitial edema and shuntlike physiology developing at the extremes of involvement. In later stages, the histologic appearance is similar to ARDS, including hyaline membrane formation and thickened alveolar septa with perivascular lymphocytic-plasmocytic infiltration. In addition, there also are findings of organizing pneumonia with fibroblastic proliferation, thrombosis, and diffuse alveolar damage, a constellation of findings similar to that seen in the latter stages of ARDS.2
Although these histologic findings resemble ARDS, many patients with respiratory failure due to COVID-19 have a different physiologic profile compared with those with typical ARDS, with the most striking finding of lungs with low elastance or high compliance. From the critical care standpoint, this meant that the lungs were relatively easy to ventilate with lower peak airway and plateau pressures and low driving pressures. This condition suggested that there was relatively less lung that could be recruited with positive end expiratory pressure; therefore, a somewhat different entity from that associated with ARDS.19 These findings were often noted early in the course of respiratory failure, and although there is debate about whether this represents a different phenotype or timepoint in the spectrum of disease, it clearly represents a subset that is distinct from that which had been previously encountered.
On the other hand, the clinical features seen in those patients with COVID-19 pneumonia who progressed to advanced respiratory failure were essentially indistinguishable from those patients with traditional ARDS. Other explanations for this respiratory failure have included a disrupted vasoregulatory response to hypoxemia with failed hypoxic vasoconstriction, intravascular microthrombi, and impaired diffusion, all contributing to impaired gas exchange and hypoxemia.19-21 This can lead to shuntlike conditions that neither respond well to supplemental oxygen nor manifest the type of physiologic response seen with other causes of hypoxemia.
The severity of hypoxemia manifested by this patient may have elicited additional findings of respiratory distress, such as dyspnea and tachypnea. However, in patients with severe COVID-19 pneumonia, dyspnea was not a universal finding, reported in the 20 to 60% range of cohorts, higher in those with ARDS and mechanical ventilation, although some report near universal dyspnea in their series.1,4,8,22,23 Tachypnea is another symptom of interest. Using a threshold of > 24 breaths/min, tachypnea was noted in 16 to 29% of patients with a much greater proportion (63%) in nonsurvivors.6,24 Several explanations have been proposed for the discordance between the presence and severity of hypoxemia and lack of symptoms of dyspnea and tachypnea. It is important to recognize that misclassification of the severity of hypoxemia can occur due to technical issues and potential errors involving pulse oximetry measurement and shifts in the oxyhemoglobin dissociation curve. However, this is more pertinent for those with mild disease as the severity of hypoxemia in severe pneumonia is beyond what can be attributed to technical issues.
More important, the ventilatory response curve to hypoxemia may not be normal for some patients, blunted by as much as 50% in older patients, especially in those with diabetes mellitus.7,25,26 In addition, the ventilatory response varies widely even among normal individuals. This would translate to lower levels of minute ventilation (less tachypnea or respiratory effort) with hypoxemia. Hypocapnic hypoxemia also blunts the ventilatory response to hypoxemia. Subjects do not increase their minute ventilation if the PaCO2 remains low despite oxygen desaturation to < 70%, especially if PaCO2 < 30 mm Hg or alternatively, increases in minute ventilation are not seen until the PaCO2 exceeds 39 mm Hg.27 Both scenarios occur in those with COVID-19 pneumonia and provide another explanation for the absence of respiratory symptoms or signs of respiratory distress in some patients.
The observation of more compliant lungs may help in the understanding of the variable presentation of these patients. Compliant lungs do not require the increased pressure needed to achieve a specific tidal volume that, in turn, may increase the work of breathing. This may add to the explanation of seemingly paradoxical silent hypoxemia in those patients where the combination of a blunted ventilatory response, hypocapnia, shunt physiology, and normal respiratory system compliance is represented by the absence of increased breathing effort despite severe hypoxemia.
If not for the patient’s refusal of medical services, this patient quite possibly would have been intubated due to hypoxemia and health care providers’ concern for her risk of deterioration. Reported intubation and mechanical ventilation rates have varied widely from extremes of from < 5 to 88% in severely ill patients.9,22 About 75% will need oxygen, but many can be treated and recover without the need for intubation and mechanical ventilation.
As previously mentioned, options for treatment include standard and high-flow oxygen delivery, noninvasive ventilation, and awake prone ventilation. Their role in patient management has been recently outlined, and instead of an early intubation strategy, represents gradual escalation of support that may be sufficient to treat hypoxemia and avoid the need for intubation and mechanical ventilation (Table 2).
In addition, the patient’s hospital course was notable for the decline in known markers of active inflammation that mirrored the resolution of her hypoxemia and pneumonia. This included elevated lactate dehydrogenase, D-dimer, ferritin, and C-reactive protein with all but the latter rising and decreasing over 2 weeks. These findings provide additional information of the time for recovery and supports the use of these markers to monitor the course of pneumonia.
The patient declined all intervention, including oxygen, and recovered to her presumed prehospitalization condition. This experiment of nature due to unique circumstances may shed light on the natural time course of untreated hypoxemic COVID-19 pneumonia that has not previously been well appreciated. It is important to recognize that recovery occurred over 2 weeks. This is close to the observed and expected time for recovery that has been reported for those with severe COVID-19 pneumonia.
Conclusions
Since the emergence of the COVID-19, evidence has accumulated for the benefit of several adjunctive therapies in the treatment of this type of pneumonia, with corticosteroids providing a mortality benefit. Although unknown whether this patient’s experience can be generalized to others or whether it represents her unique response, this case provides another perspective for comparison of treatments and reinforces the need for prospective, randomized clinical trials to establish treatment efficacy. The exact nature of silent hypoxemia of COVID-19 remains incompletely understood; however, this case highlights the importance of treating the individual instead of clinical markers and provides a time course for recovery from pneumonia and severe hypoxemia that occurs without oxygen or any other treatment over about 2 weeks.
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
1. Ioannou GN, Locke E, Green P, et al. Risk factors for hospitalization, mechanical ventilation, or death among 10131 US veterans with SARS-CoV-2 infection. JAMA Netw Open. 2020;3(9):e2022310. doi:10.1001/jamanetworkopen.2020.22310
2. Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, transmission, diagnosis, and treatment of coronavirus disease 2019 (COVID-19): a review. JAMA. 2020;324(8):782-793. doi:10.1001/jama.2020.12839
3. Alhazzani W, Moller MH, Arabi YM, et al. Surviving sepsis campaign: guidelines on the management of critically ill adults with coronavirus disease 2019 (COVID-19). Crit Care Med. 2020;48(6):e440-e469. doi:10.1097/CCM.0000000000004363
4. Ziehr DR, Alladina J, Petri CR, et al. Respiratory pathophysiology of mechanically ventilated patients with COVID-19: a cohort study. Am J Respir Crit Care Med. 2020;201(12):1560-1564. doi:10.1164/rccm.202004-1163LE
5. Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-1242. doi:10.1001/jama.2020.2648
6. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-1062. doi:10.1016/S01406736(20)30566-3
7. Tobin MJ, Laghi F, Jubran A. Why COVID-19 silent hypoxemia is baffling to physicians. Am J Respir Crit Care Med. 2020;202(3):356-360. doi:10.1164/rccm.202006-2157CP
8. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708-1720. doi:10.1056/NEJMoa2002032
9. Grasselli G, Zangrillo A, Zanella A, et al. Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. JAMA. 2020;323(16):1574-1581. doi:10.1001/jama.2020.5394
10. Raoof S, Nava S, Carpati C, Hill NS. High-flow, noninvasive ventilation and awake (nonintubation) proning in patients with coronavirus disease 2019 with respiratory failure. Chest. 2020;158(5):1992-2002. doi:10.1016/j.chest.2020.07.013
11. Ackermann M, Mentzer SJ, Jonigk D. Pulmonary vascular pathology in COVID-19. Reply. N Engl J Med. 2020;383(9):888-889. doi:10.1056/NEJMc2022068
12. McDonough G, Khaing P, Treacy T, McGrath C, Yoo EJ. The use of high-flow nasal oxygen in the ICU as a first-line therapy for acute hypoxemic respiratory failure secondary to coronavirus disease 2019. Crit Care Explor. 2020;2(10):e0257. doi:10.1097/CCE.0000000000000257
13. Hernandez-Romieu AC, Adelman MW, et al. Timing of intubation and mortality among critically ill coronavirus disease 2019 patients: a single-center cohort study. Crit Care Med. 2020;48(11):e1045-e1053. doi:10.1097/CCM.0000000000004600
14. Cummings MJ, Baldwin MR, Abrams D, et al. Epidemiology, clinical course, and outcomes of critically ill adults with COVID-19 in New York City: a prospective cohort study. Lancet. 2020;395(10239):1763-1770. doi:10.1016/S0140-6736(20)31189-2
15. Dhont S, Derom E, Van Braeckel E, Depuydt P, Lambrecht BN. The pathophysiology of ‘happy’ hypoxemia in COVID-19. Respir Res. 2020;21(1):198. doi:10.1186/s12931-020-01462-5
16. Wilkerson RG, Adler JD, Shah NG, Brown R. Silent hypoxia: a harbinger of clinical deterioration in patients with COVID-19. Am J Emerg Med. 2020;38(10):2243.e5-2243.e6. doi:10.1016/j.ajem.2020.05.044
17. Gong J, Ou J, Qiu X, et al. A tool for early prediction of severe coronavirus disease 2019 (COVID-19): a multicenter study using the risk nomogram in Wuhan and Guangdong, China. Clin Infect Dis. 2020;71(15):833-840. doi:10.1093/cid/ciaa443
18. Force ADT, Ranieri VM, Rubenfeld GD, et al. Acute respiratory distress syndrome: the Berlin Definition. JAMA. 2012;307(23):2526-2533. doi:10.1001/jama.2012.5669
19. Marini JJ, Gattinoni L. Management of COVID-19 respiratory distress. JAMA. 2020;323(22):2329-2330. doi:10.1001/jama.2020.6825
20. Schaller T, Hirschbuhl K, Burkhardt K, et al. Postmortem examination of patients with COVID-19. JAMA. 2020;323(24):2518-2520. doi:10.1001/jama.2020.8907
21. Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432
22. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med. 2020;180(7):934-943. doi:10.1001/jamainternmed.2020.0994. Published correction appeared May 11, 2020. Errors in data and units of measure. doi:10.1001/jamainternmed.2020.1429
23. Yang J, Zheng Y, Gou X, et al. Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2: a systematic review and meta-analysis. Int J Infect Dis. 2020;94:91-95. doi:10.1016/j.ijid.2020.03.017
24. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-2059. doi:10.1001/jama.2020.6775
25. Tobin MJ, Jubran A, Laghi F. Misconceptions of pathophysiology of happy hypoxemia and implications for management of COVID-19. Respir Res. 2020;21(1):249. doi:10.1186/s12931-020-01520-y
26. Bickler PE, Feiner JR, Lipnick MS, McKleroy W. “Silent” presentation of hypoxemia and cardiorespiratory compensation in COVID-19. Anesthesiology. 2020;134(2):262-269. doi:10.1097/ALN.0000000000003578
27. Jounieaux V, Parreira VF, Aubert G, Dury M, Delguste P, Rodenstein DO. Effects of hypocapnic hyperventilation on the response to hypoxia in normal subjects receiving intermittent positive-pressure ventilation. Chest. 2002;121(4):1141-1148. doi:10.1378/chest.121.4.1141
Bariatric surgery may cut cancer in obesity with liver disease
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
In a large cohort of insured working adults with severe obesity and nonalcoholic fatty liver disease (NAFLD), the rate of incident cancer was lower during a 10-month median follow-up period among those who underwent bariatric surgery. The rate was especially lower with regard to obesity-related cancers. The risk reduction was greater among patients with cirrhosis.
Among almost 100,000 patients with severe obesity (body mass index >40 kg/m2) and NAFLD, those who underwent bariatric surgery had an 18% and 35% lower risk of developing any cancer or obesity-related cancer, respectively.
Bariatric surgery was associated with a significantly lower risk of being diagnosed with colorectal, pancreatic, endometrial, and thyroid cancer, as well as hepatocellular carcinoma and multiple myeloma (all obesity-related cancers). The findings are from an observational study by Vinod K. Rustgi, MD, MBA, and colleagues, which was published online March 17, 2021, in Gastroenterology.
It was not surprising that bariatric surgery is effective in reducing the malignancy rate among patients with cirrhosis, the researchers wrote, because the surgery results in long-term weight loss, resolution of nonalcoholic steatohepatitis (NASH), and regression of fibrosis.
“Cirrhosis can happen from fatty liver disease or NASH,” Dr. Rustgi, a hepatologist at Robert Wood Johnson Medical School, New Brunswick, N.J., explained to this news organization. “It’s becoming the fastest growing indication for liver transplant, but also the reason for increased rates of hepatocellular carcinoma.”
Current treatment for patients with obesity and fatty liver disease begins with lifestyle changes to lose weight, he continued. “As people lose 10% of their weight, they actually start to see regression of fibrosis in the liver that is correlated with [lower rates of] malignancy outcomes and other deleterious outcomes.” But long-lasting weight loss is extremely difficult to achieve.
Future studies “may identify new targets and treatments, such as antidiabetic-, satiety-, or GLP-1-based medications, for chemoprevention in NAFLD/NASH,” the investigators suggested. However, pharmaceutical agents will likely be very expensive when they eventually get marketed, Dr. Rustgi observed.
Although “bariatric surgery is a more aggressive approach than lifestyle modifications, surgery may provide additional benefits, such as improved quality of life and decreased long-term health care costs,” he and his coauthors concluded.
Rising rates of fatty liver disease, obesity
An estimated 30% of the population of the United States has NAFLD, the most common chronic liver disease, the researchers noted in their article. The prevalence of NAFLD increased 2.8-fold in the United States between 2003 and 2011, in parallel with increasing obesity.
NAFLD is more common among male patients with obesity and diabetes and Hispanic patients; “70% of [patients with diabetes] may have fatty liver disease, according to certain surveys,” Dr. Rustgi noted.
Cancer is the second greatest cause of mortality among patients with obesity and NAFLD, he continued, after cardiovascular disease. Cancer mortality is higher than mortality from liver disease.
Obesity-related cancers include adenocarcinoma of the esophagus, cancers of the breast (in postmenopausal women), colon, rectum, endometrium (corpus uterus), gallbladder, gastric cardia, kidney (renal cell), liver, ovary, pancreas, and thyroid, as well as meningioma and multiple myeloma, according to a 2016 report from the International Agency for Research on Cancer working group.
Obesity-related cancer accounted for 40% of all cancer in the United States in 2014 – 55% of cancers in women, and 24% of cancers in men, according to a study published in Morbidity and Mortality Weekly Report in 2017, as previously reported by this news organization.
Several studies, including one presented at Obesity Week in 2019 and later published, have shown that bariatric surgery is linked with a lower risk for cancer in general populations.
One meta-analysis reported that NAFLD is an independent risk factor for cholangiocarcinoma and colorectal, breast, gastric, pancreatic, prostate, and esophageal cancers. In another study, NAFLD was associated with a twofold increased risk for hepatocellular carcinoma and uterine, stomach, pancreatic, and colon cancers, Dr. Rustgi and colleagues noted.
Until now, the impact of bariatric surgery on the risk for cancer among patients with obesity and NAFLD was unknown.
Does bariatric surgery curb cancer risk in liver disease?
The researchers examined insurance claims data from the national MarketScan database from Jan. 1, 2007, to Dec. 31, 2017, for patients aged 18-64 years who had health insurance from 350 employers and 100 insurers. They identified 98,090 patients with severe obesity who were newly diagnosed with NAFLD during 2008-2017.
Roughly a third of the cohort (33,435 patients) underwent bariatric surgery. From 2008 to 2017, laparoscopic sleeve gastrectomies increased from 4% of bariatric procedures to 68% of all surgeries. Laparoscopic adjustable gastric band and laparoscopic Roux-en-Y gastric bypass procedures fell from 35% to less than 1% and from 49% to 28%, respectively.
Patients who underwent bariatric surgery were younger (mean age, 44 vs. 46 years), were more likely to be women (74% vs. 62%), and were less likely to have a history of smoking (6% vs. 10%).
During a mean follow-up of 22 months (and a median follow-up of 10 months), there were 911 incident cases of obesity-related cancers. These included cancer of the colon (116 cases), rectum (15), breast (in postmenopausal women; 131), kidney (120), esophagus (16), gastric cardia (8), gallbladder (4), pancreas (44), ovaries (74), endometrium (135), and thyroid (143), as well as hepatocellular carcinoma (49), multiple myeloma (50), and meningioma (6). There were 1,912 incident cases of other cancers, such as brain and lung cancers and leukemia.
A total of 258 patients who underwent bariatric surgery developed an obesity-related cancer (an incidence of 3.83 per 1,000 person-years), compared with 653 patients who did not have bariatric surgery (an incidence of 5.63 per 1,000 person-years).
The researchers noted that study limitations include the fact that it was restricted to privately insured individuals aged 18-64 years with severe obesity. In addition, “the short median follow-up may underestimate the full effect of bariatric surgery on cancer risk,” they wrote.
The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.