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Looking to Orlando for CHEST Annual Meeting 2021
Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.
For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.
Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
Conference center and hotels
CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.
Visiting local attractions
You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.
When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.
Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.
And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.
Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.
Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.
For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.
Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
Conference center and hotels
CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.
Visiting local attractions
You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.
When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.
Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.
And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.
Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.
Thinking about best option for attending CHEST 2021 – in-person or online? There are advantages to both.
For attendees who can’t travel because of restrictions, you will have access to all the learning that will take place from Oct 17-20 at CHEST 2021. You can view the sessions through live streaming and access them on demand. CHEST is building an even better delivery platform based on the highly successful online conference last year. Compete in the Players Hub and take part in simulations. We watched last year as participants shared images on social media, showing how they joined the conference. If online is the best option for you, CHEST 2021 will deliver all the learning whenever you can attend.
Joining us in Orlando provides you the opportunity to network with your colleagues, discuss and learn informally, stop by the poster presentations, and visit with exhibitors to hear what’s new to help you in your clinical practice.
Conference center and hotels
CHEST 2021 will be held at the Orange County Convention Center, which has 1.1 million square feet of meeting and exhibition space. This means ample room for social distancing and the ability to adhere to CDC safety protocols. We anticipate there will be changes in guidelines as vaccinations roll out across the country, but CHEST is planning based on procedures currently in place. And we are taking full advantage of all the square footage with wider pathways in the exhibit hall. The Orange County Convention Center is surrounded by hotels, four of them connecting directly to the convention center. Hilton Orlando will serve as the official conference hotel.
Visiting local attractions
You don’t go to Orlando without having a few destinations in mind. If you are planning to visit Disney World, Universal Studio, or SeaWorld, reservations are required. Each park has implemented a reservation system requiring guests and pass members to secure a specific day for their visit in advance. All ticket holders – including single day visitors, multi-day ticket holders, group ticket holders, complimentary ticket holders, seasonal and annual pass members and Fun Card holders – are required to make a reservation at each park before they visit. This is to limit the total number of people in the parks at one time. Same-day reservations may be possible but should not be counted on if visiting the parks is high on your list of things to do.
When it comes to dining and shopping, International Drive – which encompasses the Orange County Convention Center – has a diverse selection of restaurants and entertainment options, ensuring something for everyone. Whether it’s eating at the AAA Four Diamond restaurants at Rosen Shingle Creek or going casual and enjoying the authentically prepared and internationally inspired foods at the Wheelhouse in ICON Park, you’ll find something that satisfies.
Looking for something different? Try an airboat ride across the wetlands of central Florida. See alligators, turtles, birds, and more in their natural environment. Trips include day tours and night adventures. Or take a guided cruise through three of the seven lakes and two narrow canals on the tranquil Winter Park chain.
And, if a few hours in the sunshine chasing a little white ball are to your liking, just down the road from the convention center is a newly redesigned championship golf course by Arnold Palmer Design Company, the Shingle Creek Golf Club. Bring your clubs or rent them at the course.
Grab your friends and colleagues for some fun and try out a few of these places. Maybe even invite the family to join you before or after the conference, and enjoy the getaway.
Negative results when immunotherapy was added to chemoradiotherapy
The JAVELIN Head and Neck 100 trial randomly assigned 697 patients who had already undergone chemoradiotherapy for locally advanced, untreated disease to receive either avelumab or placebo.
This was the first phase 3 trial in which an immune checkpoint inhibitor was given concurrently with radiotherapy in addition to chemotherapy for any indication, noted the researchers. Checkpoint inhibitors have proved effective for recurrent or metastatic disease after standard options have failed. The current trial was one of the few trials to combine a checkpoint inhibitor with standard-of-care treatment in the first-line setting.
Not only did avelumab fail to improve outcomes, but there was also a trend for better progression-free survival (PFS) in the placebo arm, suggesting that avelumab may have had an “antagonistic effect,” the team reports.
Although not statistically significant, survival curves separated in favor of placebo. There was no obvious explanation for what happened, said lead investigator Nancy Lee, MD, of Memorial Sloan Kettering Cancer Center, New York.
“Be very careful when you are thinking about immunotherapy with fractionated radiotherapy,” Dr. Lee said in an interview.
The trial was terminated early for futility. The results were published online in The Lancet Oncology.
Possible detrimental effect?
The trial was conducted in patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity. Overall, 66% of patients had human papillomavirus (HPV)–negative disease, which is associated with poorer prognosis. The rest had HPV-positive disease.
Participants received either avelumab at 10 mg/kg intravenously or placebo along with cisplatin every 3 weeks and 70 Gy of intensity-modulated radiotherapy delivered in 35 fractions during the 9-week concurrent chemoradiotherapy phase of the trial. This was followed by avelumab or placebo maintenance for up to 12 months.
At a median follow-up of almost 15 months, the median PFS was not reached in the avelumab arm (118 events; 95% confidence interval, 16.9 months – not estimable) or in the placebo arm (106 events; 95% CI, 23 months – not estimable).
There was a hint of PFS benefit in a subgroup of 36 patients with tumors showing high PD-LI expression who were taking avelumab.
However, the overall results show that PFS (hazard ratio [HR], 1.21; 95% CI, .93-1.57; P = .920) and overall survival (HR, 1.31; 95% CI, 0.93–1.85; P = .937) trended in favor of placebo.
The findings cannot be explained by increased toxicity in the avelumab arm because there were no substantial safety differences in comparison with placebo, the researchers said.
Concurrent chemotherapy was probably not a problem either. There are robust data on the use of avelumab and other checkpoint inhibitors in combination with chemotherapy for numerous oncology indications. Two such drugs – pembrolizumab and nivolumab – are approved for recurrent or metastatic squamous cell head and neck cancer in combination with chemotherapy.
Dr. Lee suspects the findings could be due to a previously unrecognized negative interaction between avelumab and the high-volume fractionated radiotherapy used for locally advanced head and neck cancer.
“With chemoradiotherapy, we are killing T cells, but we are curing patients. What’s weird is why, when we combine it with immunotherapy, it looks like there’s a detrimental effect. That’s the mystery. We are looking [at tissue samples] to find out mechanistically or biologically why we saw what we saw,” she said.
Results from similar study eagerly awaited
A nearly identical phase 3 trial is underway. The KEYNOTE-412 trial is investigating the addition of pembrolizumab to chemoradiotherapy in the first-line treatment of locally advanced squamous cell head and neck cancer.
If this study also suggests worse survival with the immune checkpoint inhibitor, it’s unlikely there was something specific about avelumab that accounts for the JAVELIN findings, and “we can say we shouldn’t consider using immunotherapy with radiation at all,” Dr. Lee said.
“It could be that there is a detrimental effect of the combination of checkpoint inhibitors with definitive radiotherapy,” said Sjoukje Oosting, MD, PhD, medical oncologist at University Medical Center Groningen, the Netherlands. She was commenting after the JAVELIN results with avelumab were presented at a conference last year and said she now “eagerly awaits” the results with pembrolizumab.
For the time being, Dr. Lee said, “We have to be cautious.” Checkpoint inhibitors might still prove useful in some relationship to first-line chemoradiotherapy.
Studies are underway. One trial is investigating the adjuvant use of immunotherapy after upfront chemoradiotherapy for head and neck cancer.
The JAVELIN trial of avelumab was funded by Pfizer and Merck. The KEYNOTE-412 trial of pembrolizumab is funded by Merck. Dr. Lee is an adviser for and has received research funding from both companies. Dr. Oosting has received research grants from Celldex and Novartis.
A version of this article first appeared on Medscape.com.
The JAVELIN Head and Neck 100 trial randomly assigned 697 patients who had already undergone chemoradiotherapy for locally advanced, untreated disease to receive either avelumab or placebo.
This was the first phase 3 trial in which an immune checkpoint inhibitor was given concurrently with radiotherapy in addition to chemotherapy for any indication, noted the researchers. Checkpoint inhibitors have proved effective for recurrent or metastatic disease after standard options have failed. The current trial was one of the few trials to combine a checkpoint inhibitor with standard-of-care treatment in the first-line setting.
Not only did avelumab fail to improve outcomes, but there was also a trend for better progression-free survival (PFS) in the placebo arm, suggesting that avelumab may have had an “antagonistic effect,” the team reports.
Although not statistically significant, survival curves separated in favor of placebo. There was no obvious explanation for what happened, said lead investigator Nancy Lee, MD, of Memorial Sloan Kettering Cancer Center, New York.
“Be very careful when you are thinking about immunotherapy with fractionated radiotherapy,” Dr. Lee said in an interview.
The trial was terminated early for futility. The results were published online in The Lancet Oncology.
Possible detrimental effect?
The trial was conducted in patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity. Overall, 66% of patients had human papillomavirus (HPV)–negative disease, which is associated with poorer prognosis. The rest had HPV-positive disease.
Participants received either avelumab at 10 mg/kg intravenously or placebo along with cisplatin every 3 weeks and 70 Gy of intensity-modulated radiotherapy delivered in 35 fractions during the 9-week concurrent chemoradiotherapy phase of the trial. This was followed by avelumab or placebo maintenance for up to 12 months.
At a median follow-up of almost 15 months, the median PFS was not reached in the avelumab arm (118 events; 95% confidence interval, 16.9 months – not estimable) or in the placebo arm (106 events; 95% CI, 23 months – not estimable).
There was a hint of PFS benefit in a subgroup of 36 patients with tumors showing high PD-LI expression who were taking avelumab.
However, the overall results show that PFS (hazard ratio [HR], 1.21; 95% CI, .93-1.57; P = .920) and overall survival (HR, 1.31; 95% CI, 0.93–1.85; P = .937) trended in favor of placebo.
The findings cannot be explained by increased toxicity in the avelumab arm because there were no substantial safety differences in comparison with placebo, the researchers said.
Concurrent chemotherapy was probably not a problem either. There are robust data on the use of avelumab and other checkpoint inhibitors in combination with chemotherapy for numerous oncology indications. Two such drugs – pembrolizumab and nivolumab – are approved for recurrent or metastatic squamous cell head and neck cancer in combination with chemotherapy.
Dr. Lee suspects the findings could be due to a previously unrecognized negative interaction between avelumab and the high-volume fractionated radiotherapy used for locally advanced head and neck cancer.
“With chemoradiotherapy, we are killing T cells, but we are curing patients. What’s weird is why, when we combine it with immunotherapy, it looks like there’s a detrimental effect. That’s the mystery. We are looking [at tissue samples] to find out mechanistically or biologically why we saw what we saw,” she said.
Results from similar study eagerly awaited
A nearly identical phase 3 trial is underway. The KEYNOTE-412 trial is investigating the addition of pembrolizumab to chemoradiotherapy in the first-line treatment of locally advanced squamous cell head and neck cancer.
If this study also suggests worse survival with the immune checkpoint inhibitor, it’s unlikely there was something specific about avelumab that accounts for the JAVELIN findings, and “we can say we shouldn’t consider using immunotherapy with radiation at all,” Dr. Lee said.
“It could be that there is a detrimental effect of the combination of checkpoint inhibitors with definitive radiotherapy,” said Sjoukje Oosting, MD, PhD, medical oncologist at University Medical Center Groningen, the Netherlands. She was commenting after the JAVELIN results with avelumab were presented at a conference last year and said she now “eagerly awaits” the results with pembrolizumab.
For the time being, Dr. Lee said, “We have to be cautious.” Checkpoint inhibitors might still prove useful in some relationship to first-line chemoradiotherapy.
Studies are underway. One trial is investigating the adjuvant use of immunotherapy after upfront chemoradiotherapy for head and neck cancer.
The JAVELIN trial of avelumab was funded by Pfizer and Merck. The KEYNOTE-412 trial of pembrolizumab is funded by Merck. Dr. Lee is an adviser for and has received research funding from both companies. Dr. Oosting has received research grants from Celldex and Novartis.
A version of this article first appeared on Medscape.com.
The JAVELIN Head and Neck 100 trial randomly assigned 697 patients who had already undergone chemoradiotherapy for locally advanced, untreated disease to receive either avelumab or placebo.
This was the first phase 3 trial in which an immune checkpoint inhibitor was given concurrently with radiotherapy in addition to chemotherapy for any indication, noted the researchers. Checkpoint inhibitors have proved effective for recurrent or metastatic disease after standard options have failed. The current trial was one of the few trials to combine a checkpoint inhibitor with standard-of-care treatment in the first-line setting.
Not only did avelumab fail to improve outcomes, but there was also a trend for better progression-free survival (PFS) in the placebo arm, suggesting that avelumab may have had an “antagonistic effect,” the team reports.
Although not statistically significant, survival curves separated in favor of placebo. There was no obvious explanation for what happened, said lead investigator Nancy Lee, MD, of Memorial Sloan Kettering Cancer Center, New York.
“Be very careful when you are thinking about immunotherapy with fractionated radiotherapy,” Dr. Lee said in an interview.
The trial was terminated early for futility. The results were published online in The Lancet Oncology.
Possible detrimental effect?
The trial was conducted in patients with locally advanced squamous cell carcinoma of the oropharynx, hypopharynx, larynx, or oral cavity. Overall, 66% of patients had human papillomavirus (HPV)–negative disease, which is associated with poorer prognosis. The rest had HPV-positive disease.
Participants received either avelumab at 10 mg/kg intravenously or placebo along with cisplatin every 3 weeks and 70 Gy of intensity-modulated radiotherapy delivered in 35 fractions during the 9-week concurrent chemoradiotherapy phase of the trial. This was followed by avelumab or placebo maintenance for up to 12 months.
At a median follow-up of almost 15 months, the median PFS was not reached in the avelumab arm (118 events; 95% confidence interval, 16.9 months – not estimable) or in the placebo arm (106 events; 95% CI, 23 months – not estimable).
There was a hint of PFS benefit in a subgroup of 36 patients with tumors showing high PD-LI expression who were taking avelumab.
However, the overall results show that PFS (hazard ratio [HR], 1.21; 95% CI, .93-1.57; P = .920) and overall survival (HR, 1.31; 95% CI, 0.93–1.85; P = .937) trended in favor of placebo.
The findings cannot be explained by increased toxicity in the avelumab arm because there were no substantial safety differences in comparison with placebo, the researchers said.
Concurrent chemotherapy was probably not a problem either. There are robust data on the use of avelumab and other checkpoint inhibitors in combination with chemotherapy for numerous oncology indications. Two such drugs – pembrolizumab and nivolumab – are approved for recurrent or metastatic squamous cell head and neck cancer in combination with chemotherapy.
Dr. Lee suspects the findings could be due to a previously unrecognized negative interaction between avelumab and the high-volume fractionated radiotherapy used for locally advanced head and neck cancer.
“With chemoradiotherapy, we are killing T cells, but we are curing patients. What’s weird is why, when we combine it with immunotherapy, it looks like there’s a detrimental effect. That’s the mystery. We are looking [at tissue samples] to find out mechanistically or biologically why we saw what we saw,” she said.
Results from similar study eagerly awaited
A nearly identical phase 3 trial is underway. The KEYNOTE-412 trial is investigating the addition of pembrolizumab to chemoradiotherapy in the first-line treatment of locally advanced squamous cell head and neck cancer.
If this study also suggests worse survival with the immune checkpoint inhibitor, it’s unlikely there was something specific about avelumab that accounts for the JAVELIN findings, and “we can say we shouldn’t consider using immunotherapy with radiation at all,” Dr. Lee said.
“It could be that there is a detrimental effect of the combination of checkpoint inhibitors with definitive radiotherapy,” said Sjoukje Oosting, MD, PhD, medical oncologist at University Medical Center Groningen, the Netherlands. She was commenting after the JAVELIN results with avelumab were presented at a conference last year and said she now “eagerly awaits” the results with pembrolizumab.
For the time being, Dr. Lee said, “We have to be cautious.” Checkpoint inhibitors might still prove useful in some relationship to first-line chemoradiotherapy.
Studies are underway. One trial is investigating the adjuvant use of immunotherapy after upfront chemoradiotherapy for head and neck cancer.
The JAVELIN trial of avelumab was funded by Pfizer and Merck. The KEYNOTE-412 trial of pembrolizumab is funded by Merck. Dr. Lee is an adviser for and has received research funding from both companies. Dr. Oosting has received research grants from Celldex and Novartis.
A version of this article first appeared on Medscape.com.
Low-risk adenomas may not elevate risk of CRC-related death
Unlike high-risk adenomas (HRAs), low-risk adenomas (LRAs) have a minimal association with risk of metachronous colorectal cancer (CRC), and no relationship with odds of metachronous CRC-related mortality, according to a meta-analysis of more than 500,000 individuals.
These findings should impact surveillance guidelines and make follow-up the same for individuals with LRAs or no adenomas, reported lead author Abhiram Duvvuri, MD, of the division of gastroenterology and hepatology at the University of Kansas, Kansas City, and colleagues. Currently, the United States Multi-Society Task Force on Colorectal Cancer advises colonoscopy intervals of 3 years for individuals with HRAs, 7-10 years for those with LRAs, and 10 years for those without adenomas.
“The evidence supporting these surveillance recommendations for clinically relevant endpoints such as cancer and cancer-related deaths among patients who undergo adenoma removal, particularly LRA, is minimal, because most of the evidence was based on the surrogate risk of metachronous advanced neoplasia,” the investigators wrote in Gastroenterology.
To provide more solid evidence, the investigators performed a systematic review and meta-analysis, ultimately analyzing 12 studies with data from 510,019 individuals at a mean age of 59.2 years. All studies reported rates of LRA, HRA, or no adenoma at baseline colonoscopy, plus incidence of metachronous CRC and/or CRC-related mortality. With these data, the investigators determined incidence of metachronous CRC and CRC-related mortality for each of the adenoma groups and also compared these incidences per 10,000 person-years of follow-up across groups.
After a mean follow-up of 8.5 years, patients with HRAs had a significantly higher rate of CRC compared with patients who had LRAs (13.81 vs. 4.5; odds ratio, 2.35; 95% confidence interval, 1.72-3.20) or no adenomas (13.81 vs. 3.4; OR, 2.92; 95% CI, 2.31-3.69). Similarly, but to a lesser degree, LRAs were associated with significantly greater risk of CRC than that of no adenomas (4.5 vs. 3.4; OR, 1.26; 95% CI, 1.06-1.51).
Data on CRC- related mortality further supported these minimal risk profiles because LRAs did not significantly increase the risk of CRC-related mortality compared with no adenomas (OR, 1.15; 95% CI, 0.76-1.74). In contrast, HRAs were associated with significantly greater risk of CRC-related death than that of both LRAs (OR, 2.48; 95% CI, 1.30-4.75) and no adenomas (OR, 2.69; 95% CI, 1.87-3.87).
The investigators acknowledged certain limitations of their study. For one, there were no randomized controlled trials in the meta-analysis, which can introduce bias. Loss of patients to follow-up is also possible; however, the investigators noted that there was a robust sample of patients available for study outcomes all the same. There is also risk of comparability bias in that HRA and LRA groups underwent more colonoscopies; however, the duration of follow-up and timing of last colonoscopy were similar among groups. Lastly, it’s possible the patient sample wasn’t representative because of healthy screenee bias, but the investigators compared groups against general population to minimize that bias.
The investigators also highlighted several strengths of their study that make their findings more reliable than those of past meta-analyses. For one, their study is the largest of its kind to date, and involved a significantly higher number of patients with LRA and no adenomas. Also, in contrast with previous studies, CRC and CRC-related mortality were evaluated rather than advanced adenomas, they noted.
“Furthermore, we also analyzed CRC incidence and mortality in the LRA group compared with the general population, with the [standardized incidence ratio] being lower and [standardized mortality ratio] being comparable, confirming that it is indeed a low-risk group,” they wrote.
Considering these strengths and the nature of their findings, Dr. Duvvuri and colleagues called for a more conservative approach to CRC surveillance among individuals with LRAs, and more research to investigate extending colonoscopy intervals even further.
“We recommend that the interval for follow-up colonoscopy should be the same in patients with LRAs or no adenomas but that the HRA group should have a more frequent surveillance interval for CRC surveillance compared with these groups,” they concluded. “Future studies should evaluate whether surveillance intervals could be lengthened beyond 10 years in the no-adenoma and LRA groups after an initial high-quality index colonoscopy.”
One author disclosed affiliations with Erbe, Cdx Labs, Aries, and others. Dr. Duvvuri and the remaining authors disclosed no conflicts.
Unlike high-risk adenomas (HRAs), low-risk adenomas (LRAs) have a minimal association with risk of metachronous colorectal cancer (CRC), and no relationship with odds of metachronous CRC-related mortality, according to a meta-analysis of more than 500,000 individuals.
These findings should impact surveillance guidelines and make follow-up the same for individuals with LRAs or no adenomas, reported lead author Abhiram Duvvuri, MD, of the division of gastroenterology and hepatology at the University of Kansas, Kansas City, and colleagues. Currently, the United States Multi-Society Task Force on Colorectal Cancer advises colonoscopy intervals of 3 years for individuals with HRAs, 7-10 years for those with LRAs, and 10 years for those without adenomas.
“The evidence supporting these surveillance recommendations for clinically relevant endpoints such as cancer and cancer-related deaths among patients who undergo adenoma removal, particularly LRA, is minimal, because most of the evidence was based on the surrogate risk of metachronous advanced neoplasia,” the investigators wrote in Gastroenterology.
To provide more solid evidence, the investigators performed a systematic review and meta-analysis, ultimately analyzing 12 studies with data from 510,019 individuals at a mean age of 59.2 years. All studies reported rates of LRA, HRA, or no adenoma at baseline colonoscopy, plus incidence of metachronous CRC and/or CRC-related mortality. With these data, the investigators determined incidence of metachronous CRC and CRC-related mortality for each of the adenoma groups and also compared these incidences per 10,000 person-years of follow-up across groups.
After a mean follow-up of 8.5 years, patients with HRAs had a significantly higher rate of CRC compared with patients who had LRAs (13.81 vs. 4.5; odds ratio, 2.35; 95% confidence interval, 1.72-3.20) or no adenomas (13.81 vs. 3.4; OR, 2.92; 95% CI, 2.31-3.69). Similarly, but to a lesser degree, LRAs were associated with significantly greater risk of CRC than that of no adenomas (4.5 vs. 3.4; OR, 1.26; 95% CI, 1.06-1.51).
Data on CRC- related mortality further supported these minimal risk profiles because LRAs did not significantly increase the risk of CRC-related mortality compared with no adenomas (OR, 1.15; 95% CI, 0.76-1.74). In contrast, HRAs were associated with significantly greater risk of CRC-related death than that of both LRAs (OR, 2.48; 95% CI, 1.30-4.75) and no adenomas (OR, 2.69; 95% CI, 1.87-3.87).
The investigators acknowledged certain limitations of their study. For one, there were no randomized controlled trials in the meta-analysis, which can introduce bias. Loss of patients to follow-up is also possible; however, the investigators noted that there was a robust sample of patients available for study outcomes all the same. There is also risk of comparability bias in that HRA and LRA groups underwent more colonoscopies; however, the duration of follow-up and timing of last colonoscopy were similar among groups. Lastly, it’s possible the patient sample wasn’t representative because of healthy screenee bias, but the investigators compared groups against general population to minimize that bias.
The investigators also highlighted several strengths of their study that make their findings more reliable than those of past meta-analyses. For one, their study is the largest of its kind to date, and involved a significantly higher number of patients with LRA and no adenomas. Also, in contrast with previous studies, CRC and CRC-related mortality were evaluated rather than advanced adenomas, they noted.
“Furthermore, we also analyzed CRC incidence and mortality in the LRA group compared with the general population, with the [standardized incidence ratio] being lower and [standardized mortality ratio] being comparable, confirming that it is indeed a low-risk group,” they wrote.
Considering these strengths and the nature of their findings, Dr. Duvvuri and colleagues called for a more conservative approach to CRC surveillance among individuals with LRAs, and more research to investigate extending colonoscopy intervals even further.
“We recommend that the interval for follow-up colonoscopy should be the same in patients with LRAs or no adenomas but that the HRA group should have a more frequent surveillance interval for CRC surveillance compared with these groups,” they concluded. “Future studies should evaluate whether surveillance intervals could be lengthened beyond 10 years in the no-adenoma and LRA groups after an initial high-quality index colonoscopy.”
One author disclosed affiliations with Erbe, Cdx Labs, Aries, and others. Dr. Duvvuri and the remaining authors disclosed no conflicts.
Unlike high-risk adenomas (HRAs), low-risk adenomas (LRAs) have a minimal association with risk of metachronous colorectal cancer (CRC), and no relationship with odds of metachronous CRC-related mortality, according to a meta-analysis of more than 500,000 individuals.
These findings should impact surveillance guidelines and make follow-up the same for individuals with LRAs or no adenomas, reported lead author Abhiram Duvvuri, MD, of the division of gastroenterology and hepatology at the University of Kansas, Kansas City, and colleagues. Currently, the United States Multi-Society Task Force on Colorectal Cancer advises colonoscopy intervals of 3 years for individuals with HRAs, 7-10 years for those with LRAs, and 10 years for those without adenomas.
“The evidence supporting these surveillance recommendations for clinically relevant endpoints such as cancer and cancer-related deaths among patients who undergo adenoma removal, particularly LRA, is minimal, because most of the evidence was based on the surrogate risk of metachronous advanced neoplasia,” the investigators wrote in Gastroenterology.
To provide more solid evidence, the investigators performed a systematic review and meta-analysis, ultimately analyzing 12 studies with data from 510,019 individuals at a mean age of 59.2 years. All studies reported rates of LRA, HRA, or no adenoma at baseline colonoscopy, plus incidence of metachronous CRC and/or CRC-related mortality. With these data, the investigators determined incidence of metachronous CRC and CRC-related mortality for each of the adenoma groups and also compared these incidences per 10,000 person-years of follow-up across groups.
After a mean follow-up of 8.5 years, patients with HRAs had a significantly higher rate of CRC compared with patients who had LRAs (13.81 vs. 4.5; odds ratio, 2.35; 95% confidence interval, 1.72-3.20) or no adenomas (13.81 vs. 3.4; OR, 2.92; 95% CI, 2.31-3.69). Similarly, but to a lesser degree, LRAs were associated with significantly greater risk of CRC than that of no adenomas (4.5 vs. 3.4; OR, 1.26; 95% CI, 1.06-1.51).
Data on CRC- related mortality further supported these minimal risk profiles because LRAs did not significantly increase the risk of CRC-related mortality compared with no adenomas (OR, 1.15; 95% CI, 0.76-1.74). In contrast, HRAs were associated with significantly greater risk of CRC-related death than that of both LRAs (OR, 2.48; 95% CI, 1.30-4.75) and no adenomas (OR, 2.69; 95% CI, 1.87-3.87).
The investigators acknowledged certain limitations of their study. For one, there were no randomized controlled trials in the meta-analysis, which can introduce bias. Loss of patients to follow-up is also possible; however, the investigators noted that there was a robust sample of patients available for study outcomes all the same. There is also risk of comparability bias in that HRA and LRA groups underwent more colonoscopies; however, the duration of follow-up and timing of last colonoscopy were similar among groups. Lastly, it’s possible the patient sample wasn’t representative because of healthy screenee bias, but the investigators compared groups against general population to minimize that bias.
The investigators also highlighted several strengths of their study that make their findings more reliable than those of past meta-analyses. For one, their study is the largest of its kind to date, and involved a significantly higher number of patients with LRA and no adenomas. Also, in contrast with previous studies, CRC and CRC-related mortality were evaluated rather than advanced adenomas, they noted.
“Furthermore, we also analyzed CRC incidence and mortality in the LRA group compared with the general population, with the [standardized incidence ratio] being lower and [standardized mortality ratio] being comparable, confirming that it is indeed a low-risk group,” they wrote.
Considering these strengths and the nature of their findings, Dr. Duvvuri and colleagues called for a more conservative approach to CRC surveillance among individuals with LRAs, and more research to investigate extending colonoscopy intervals even further.
“We recommend that the interval for follow-up colonoscopy should be the same in patients with LRAs or no adenomas but that the HRA group should have a more frequent surveillance interval for CRC surveillance compared with these groups,” they concluded. “Future studies should evaluate whether surveillance intervals could be lengthened beyond 10 years in the no-adenoma and LRA groups after an initial high-quality index colonoscopy.”
One author disclosed affiliations with Erbe, Cdx Labs, Aries, and others. Dr. Duvvuri and the remaining authors disclosed no conflicts.
FROM GASTROENTEROLOGY
Surveillance endoscopy in Barrett’s may perform better than expected
For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.
Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.
This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.
“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”
On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.
To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.
Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
Technology challenged by technique
The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.
“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.
The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).
“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.
“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”
The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.
“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.
The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.
For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.
Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.
This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.
“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”
On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.
To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.
Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
Technology challenged by technique
The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.
“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.
The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).
“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.
“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”
The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.
“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.
The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.
For patients with Barrett’s esophagus, surveillance endoscopy detects high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) more often than previously reported, according to a retrospective analysis of more than 1,000 patients.
Neoplasia detection rate, defined as findings on initial surveillance endoscopy, was also lower than that observed in past studies, according to lead author Lovekirat Dhaliwal, MBBS, of Mayo Clinic, Rochester, Minn., and colleagues.
This study’s findings may help define quality control benchmarks for endoscopic surveillance of Barrett’s esophagus, the investigators wrote in Clinical Gastroenterology and Hepatology. Accurate metrics are needed, they noted, because almost 9 out of 10 patients with Barrett’s esophagus present with EAC outside of a surveillance program, which “may represent missed opportunities at screening.” At the same time, a previous study by the investigators and one from another group, have suggested that 25%-33% of HGD/EAC cases may go undetected by initial surveillance endoscopy.
“Dysplasia detection in [Barrett’s esophagus] is challenging because of its patchy distribution and often subtle appearance,” the investigators noted. “Lack of compliance with recommended biopsy guidelines is also well-documented.”
On the other hand, Dr. Dhaliwal and colleagues suggested that previous studies may not accurately portray community practice and, therefore, have limited value in determining quality control metrics. A 2019 review, for instance, reported a neoplasia detection rate of 7% among patients with Barrett’s esophagus, but this finding “is composed of data from largely referral center cohorts with endoscopy performed by experienced academic gastroenterologists,” they wrote, which may lead to overestimation of such detection.
To better characterize this landscape, the investigators conducted a retrospective analysis involving 1,066 patients with Barrett’s esophagus who underwent initial surveillance endoscopy between 1991 and 2019. Approximately three out of four surveillance endoscopies (77%) were performed by gastroenterologists, while the remaining were performed by nongastroenterologists, such as family practitioners or surgeons. About 60% of patients were adequately biopsied according to the Seattle protocol.
Analysis revealed that the neoplasia detection rate was 4.9% (95% confidence interval, 3.8%-6.4%), which is less than the previously reported rate of 7%. HGD was more common than EAC (33 cases vs. 20 cases). Out of 1,066 patients, 391 without neoplasia on initial endoscopy underwent repeat endoscopy within a year. Among these individuals, HGD or EAC was detected in eight patients, which suggests that 13% of diagnoses were missed on initial endoscopy, a rate well below the previously reported range of 25%-33%.
Technology challenged by technique
The neoplasia detection rate “appeared to increase significantly from 1991 to 2019 on univariate analysis (particularly after 2000), but this was not observed on multivariate analysis,” the investigators wrote. “This was despite the introduction of high definition monitors and high resolution endoscopes in subsequent years.
“This may suggest that in a low dysplasia prevalence setting, basic techniques such as careful white light inspection of the [Barrett’s esophagus] mucosa along with targeted and Seattle protocol biopsies may be more important,” they noted.
The importance of technique may be further supported by another finding: Gastroenterologists detected neoplasia almost four times as often as did nongastroenterologists (odds ratio, 3.6; P = .0154).
“This finding is novel and may be due to additional training in endoscopy, lesion recognition, and familiarity with surveillance guidelines in gastroenterologists,” the investigators wrote. “If this finding is replicated in other cohorts, it may support recommendations for the performance of surveillance by endoscopists trained in gastrointestinal endoscopy and well-versed in surveillance guidelines.
“[U]sing neoplasia detection as a quality metric coupled with outcome measures such as missed dysplasia rates could improve adherence to established biopsy protocols and improve the quality of care to patients,” they wrote. “Ultimately, this can be an opportunity to develop a high-value, evidence-based quality metric in [Barrett’s esophagus] surveillance.”
The authors acknowledged some limitations to their study. Its retrospective design meant no one biopsy protocol could be adopted across the entire study period; however, the results were “unchanged” when restricted to the period after introduction of the Seattle protocol in 2000. The study’s long period could have left results susceptible to changing guidelines, but the neoplasia detection rates remained relatively stable over time.
“Because prior reports consisted largely of tertiary care center cohorts, our findings may reflect the absence of referral bias and be more generalizable,” the investigators wrote.
The study was funded by the National Institute of Aging and the National Cancer Institute. The investigators disclosed relationships with Celgene, Nine Point Medical, Takeda, and others.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
How physicians can provide better care to transgender patients
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
People who identify as transgender experience many health disparities, in addition to lack of access to quality care. The most commonly cited barrier is the lack of providers who are knowledgeable about transgender health care, according to past surveys.
Even those who do seek care often have unpleasant experiences. A 2015 survey conducted by the National Center for Transgender Equality found that 33% of those who saw a health care provider reported at least one unfavorable experience related to being transgender, such as being verbally harassed or refused treatment because of their gender identity. In fact, 23% of those surveyed say they did not seek health care they needed in the past year because of fear of being mistreated as a transgender person.
This interview has been edited for length and clarity.
Question: Surveys have shown that many people who identify as transgender will seek only transition care, not primary or preventive care. Why is that?
Dr. Brandt: My answer is multifactorial. Transgender patients do seek primary care – just not as readily. There’s a lot of misconceptions about health care needs for the LGBT community in general. For example, lesbian or bisexual women may be not as well informed about the need for Pap smears compared with their heterosexual counterparts. These misconceptions are further exacerbated in the transgender community.
The fact that a lot of patients seek only transition-related care, but not preventive services, such as primary care and gynecologic care, is also related to fears of discrimination and lack of education of providers. These patients are afraid when they walk into an office that they will be misgendered or their physician won’t be familiar with their health care needs.
What can clinics and clinicians do to create a safe and welcoming environment?
Dr. Brandt: It starts with educating office staff about terminology and gender identities.
A key feature of our EHR is the sexual orientation and gender identity platform, which asks questions about a patient’s gender identity, sexual orientation, sex assigned at birth, and organ inventory. These data are then found in the patient information tab and are just as relevant as their insurance status, age, and date of birth.
There are many ways a doctor’s office can signal to patients that they are inclusive. They can hang LGBTQ-friendly flags or symbols or a sign saying, “We have an anti-discrimination policy” in the waiting room. A welcoming environment can also be achieved by revising patient questionnaires or forms so that they aren’t gender-specific or binary.
Given that the patient may have limited contact with a primary care clinician, how do you prioritize what you address during the visit?
Dr. Brandt: Similar to cisgender patients, it depends initially on the age of the patient and the reason for the visit. The priorities of an otherwise healthy transgender patient in their 20s are going to be largely the same as for a cisgender patient of the same age. As patients age in the primary care world, you’re addressing more issues, such as colorectal screening, lipid disorders, and mammograms, and that doesn’t change. For the most part, the problems that you address should be specific for that age group.
It becomes more complicated when you add in factors such as hormone therapy and whether patients have had any type of gender-affirming surgery. Those things can change the usual recommendations for screening or risk assessment. We try to figure out what routine health maintenance and cancer screening a patient needs based on age and risk factors, in addition to hormone status and surgical state.
Do you think that many physicians are educated about the care of underserved populations such as transgender patients?
Dr. Brandt: Yes and no. We are definitely getting better at it. For example, the American College of Obstetricians and Gynecologists published a committee opinion highlighting transgender care. So organizations are starting to prioritize these populations and recognize that they are, in fact, underserved and they have special health care needs.
However, the knowledge gaps are still pretty big. I get calls daily from providers asking questions about how to manage patients on hormones, or how to examine a patient who has undergone a vaginoplasty. I hear a lot of horror stories from transgender patients who had their hormones stopped for absurd and medically misinformed reasons.
But I definitely think it’s getting better and it’s being addressed at all levels – the medical school level, the residency level, and the attending level. It just takes time to inform people and for people to get used to the health care needs of these patients.
What should physicians keep in mind when treating patients who identify as transgender?
Dr. Brandt: First and foremost, understanding the terminology and the difference between gender identity, sex, and sexual orientation. Being familiar with that language and being able to speak that language very comfortably and not being awkward about it is a really important thing for primary care physicians and indeed any physician who treats transgender patients.
Physicians should also be aware that any underserved population has higher rates of mental health issues, such as depression and anxiety. Obviously, that goes along with being underserved and the stigma and the disparities that exist for these patients. Having providers educate themselves about what those disparities are and how they impact a patient’s daily life and health is paramount to knowing how to treat patients.
What are your top health concerns for these patients and how do you address them?
Dr. Brandt: I think mental health and safety is probably the number one for me. About 41% of transgender adults have attempted suicide. That number is roughly 51% in transgender youth. That is an astonishing number. These patients have much higher rates of domestic violence, intimate partner violence, and sexual assault, especially trans women and trans women of color. So understanding those statistics is huge.
Obesity, smoking, and substance abuse are my next three. Again, those are things that should be addressed at any visit, regardless of the gender identity or sexual orientation of the patient, but those rates are particularly high in this population.
Fertility and long-term care for patients should be addressed. Many patients who identify as transgender are told they can’t have a family. As a primary care physician, you may see a patient before they are seen by an ob.gyn. or surgeon. Talking about what a patient’s long-term life goals are with fertility and family planning, and what that looks like for them, is a big thing for me. Other providers may not feel that’s a concern, but I believe it should be discussed before initiation of hormone therapy, which can significantly impact fertility in some patients.
Are there nuances to the physical examination that primary care physicians should be aware of when dealing with transmasculine patients vs. transfeminine patients?
Dr. Brandt: Absolutely. And this interview can’t cover the scope of those nuances. An example that comes to mind is the genital exam. For transgender women who have undergone a vaginoplasty, the pelvic exam can be very affirming. Whereas for transgender men, a gynecologic exam can significantly exacerbate dysphoria and there are ways to conduct the exam to limit this discomfort and avoid creating a traumatic experience for the patient. It’s important to be aware that the genital exam, or any type of genitourinary exam, can be either affirming or not affirming.
Sexually transmitted infections are up in the general population, and the trans population is at even higher risk. What should physicians think about when they assess this risk?
Dr. Brandt: It’s really important for primary care clinicians and for gynecologists to learn to be comfortable talking about sexual practices, because what people do behind closed doors is really a key to how to counsel patients about safe sex.
People are well aware of the need to have safe sex. However, depending on the type of sex that you’re having, what body parts go where, what is truly safe can vary and people may not know, for example, to wear a condom when sex toys are involved or that a transgender male on testosterone can become pregnant during penile-vaginal intercourse. Providers really should be very educated on the array of sexual practices that people have and how to counsel them about those. They should know how to ask patients the gender identity of their sexual partners, the sexual orientation of their partners, and what parts go where during sex.
Providers should also talk to patients about PrEP [pre-exposure prophylaxis], whether they identify as cisgender or transgender. My trans patients tend to be a lot more educated about PrEP than other patients. It’s something that many of the residents, even in a standard gynecologic clinic, for example, don’t talk to cisgender patients about because of the stigma surrounding HIV. Many providers still think that the only people who are at risk for HIV are men who have sex with men. And while those rates are higher in some populations, depending on sexual practices, those aren’t the only patients who qualify for PrEP.
Overall, in order to counsel patients about STIs and safe sexual practices, providers should learn to be comfortable talking about sex.
Do you have any strategies on how to make the appointment more successful in addressing those issues?
Dr. Brandt: Bedside manner is a hard thing to teach, and comfort in talking about sex, gender identity, and sexual orientation can vary – but there are a lot of continuing medical education courses that physicians can utilize through the World Professional Association for Transgender Health.
If providers start to notice an influx of patients who identify as transgender or if they want to start seeing transgender patients, it’s really important for them to have that training before they start interacting with patients. In all of medicine, we sort of learn as we go, but this patient population has been subjected to discrimination, violence, error, and misgendering. They have dealt with providers who didn’t understand their health care needs. While this field is evolving, knowing how to appropriately address a patient (using their correct name, pronouns, etc.) is an absolute must.
That needs to be part of a provider’s routine vernacular and not something that they sort of stumble through. You can scare a patient away as soon as they walk into the office with an uneducated front desk staff and things that are seen in the office. Seeking out those educational tools, being aware of your own deficits as a provider and the educational needs of your office, and addressing those needs is really key.
A version of this article first appeared on Medscape.com.
Steroid-refractory pneumonitis from ICIs: Experience at major centers
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
Pneumonitis is an uncommon and potentially life-threatening complication of immune checkpoint inhibitor (ICI) therapy. A fraction of patients with ICI-related pneumonitis fail to respond to initial therapy with high-dose systemic steroids.
The recently published experiences at two major cancer centers shed light on the outcomes from treatment and can provide some advice to clinicians for dealing with affected patients.
The Johns Hopkins experience
Because ICI-related pneumonitis typically improves within 48-72 hours of steroid therapy, at Johns Hopkins University, Baltimore, steroid-refractory pneumonitis is defined as pneumonitis that demonstrates no clinical improvement after high-dose corticosteroids for 2-14 days. If the immune toxicity–specialized, multidisciplinary management team implements additional immunosuppressive therapy, that is regarded as confirmatory evidence.
Aanika Balaji, a medical student at Johns Hopkins University, and colleagues retrospectively summarized the clinical course of 12 patients with ICI-related pneumonitis between 2011 and 2020. Clinical improvement with subsequent treatment was evidenced by reduction in either level of care or oxygen requirements.
Three-quarters of the patients were current or former smokers, and the same proportion had lung cancer. Most patients (91.6%) had received chemotherapy, 58.3% had prior chest radiotherapy, and 58.3% had achieved partial response or stable disease with an ICI.
Steroid-refractory ICI-related pneumonitis developed between 40 and 127 days (median, 85 days) after the first dose of ICI therapy. Subsequent immunosuppressive management included IVIg, infliximab, or the combination, in addition to ICU-level supportive care.
Among the seven patients who received IVIg alone, two patients (29%) achieved clinical improvement and hospital discharge. The remainder died.
The two patients treated with infliximab and the three patients treated with sequential IVIg and infliximab died. All deaths were attributed to ICI-related pneumonitis or infectious complications.
Overall, clinically relevant findings were:
- Steroid-refractory ICI-related pneumonitis was seen in 18.5% of patients referred for multidisciplinary care.
- Steroid-refractory ICI-related pneumonitis occurred at a median of 85 days into a patient’s ICI treatment.
- Some patients improved clinically after IVIg therapy, but mortality was high overall.
- Infliximab therapy, alone or in combination with IVIg, was ineffective.
The Memorial Sloan Kettering experience
Jason Beattie, MD, of Memorial Sloan Kettering Cancer Center, New York, and colleagues performed a retrospective study of patients who had pneumonitis after ICI therapy and/or received immune modulator therapy after corticosteroids in the setting of ICI cancer treatment.
Manual record review was performed to exclude cases of pneumonitis from other causes. The period reviewed was roughly contemporaneous with the Johns Hopkins series.
Patients with ICI-related pneumonitis were divided into “steroid refractory” (i.e., no response to high-dose corticosteroids) or “steroid resistant” (i.e., initial response, followed by worsening) categories.
The researchers identified 26 patients with ICI-related pneumonitis, all of whom had advanced malignancy (8 lung cancer, 4 malignant melanoma, 4 renal cell cancer, and 10 “other” cancers).
A majority of patients (85%) were current or former smokers, 73% had received ICI monotherapy, 35% had received prior chest radiation at a median interval of 4.9 months prior to pneumonitis onset, and 27% had preexisting pulmonary disease.
Twelve patients (46%) had steroid-refractory ICI-related pneumonitis, and 14 (54%) had steroid-resistant ICI-related pneumonitis.
The two groups differed in time to pneumonitis onset (a median of 68 days in the refractory group and 182 days in the resistant group) and time to immune modulator therapy after beginning steroids (median 7 days and 2.9 months, respectively). In the steroid-refractory cases, pneumonitis was more severe.
In addition to corticosteroids, most patients received infliximab monotherapy or infliximab with mycophenolate mofetil. In contrast to the Johns Hopkins series, IVIg was not used in the Memorial Sloan Kettering cases.
Outcomes from immune modulators were graded based on clinical evidence (progress notes, oxygen requirements, level of care, radiologic information, etc.) of resolution of pneumonitis on imaging at least 8 weeks after cessation of steroids and immune modulator therapy, durable improvement for at least 8 weeks after immune modulator therapy, transient improvement followed by pneumonitis relapse or inadequate follow-up because of death or hospice referral, or no improvement.
Ten patients (38%) had durable improvement of ICI-related pneumonitis, of whom three (12%) had complete resolution. Two of the patients with complete resolution had steroid-refractory pneumonitis, both of whom had received infliximab followed by mycophenolate mofetil.
Among the seven patients with durable improvement, four remained alive on immune modulators. Time to resolution of pneumonitis was protracted, ranging from 2.3 months to 8.4 months in the steroid-refractory patients.
Durable response was less common with steroid-refractory (25%) than steroid-resistant (50%) disease, with a significant difference in 90-day survival of 25% and 71%, respectively.
Among the 13 (50%) patients with transient improvement in ICI-related pneumonitis, 8 ultimately died, either because of recurrent ICI-related pneumonitis or infection. All three patients with no improvement from immune modulators died.
The 90-day all-cause mortality was 50%, with durable pneumonitis improvement and freedom from severe infectious complications occurring in only about a third of patients.
Lessons for clinicians
The National Comprehensive Cancer Network, the Society for Immunotherapy of Cancer, and the European Society of Medical Oncology have all published guidelines and recommendations for immunosuppression for steroid-refractory adverse events from ICIs.
Unfortunately, there is little experience with steroid-unresponsive ICI-related pneumonitis. The ideal sequence, dose, and duration of additional immune modulator therapy for ICI-related pneumonitis are unclear and may differ from the approaches to other immune-related toxicities.
This is important because, as suggested in an editorial by Margaret Gatti-Mays, MD, and James L. Gulley, MD, PhD, it is likely that ICI-related pneumonitis will be seen more in routine practice than in clinical trial populations. In addition, across all tumor types, ICI-related pneumonitis is the most common cause of ICI-associated death from toxicity.
The retrospective studies from Johns Hopkins and Memorial Sloan Kettering constitute the largest published experience with ICI-related pneumonitis and yield important clinical insights.
Uniform definitions of potentially important patient subgroups (e.g., steroid refractory vs. steroid resistant) are needed. The steroid-refractory and steroid-resistant subgroups have distinctly different clinical features and outcomes. Uniformity in the subgroup definitions would be a useful starting point from both clinical and research perspectives.
Preferred treatment choices need to be tested systematically in multi-institutional studies. Any potential impact of treatment for ICI-related pneumonitis on antitumor immune control should be identified.
Endpoints of interest need to be defined and measured prospectively. All-cause mortality after 90 days is important, but, as the authors of both reviews noted, there are vitally important narratives and differences in functionality that are completely concealed by restricting the focus to mortality.
Potential causal relationships with antecedent exposure to tobacco, radiation, intrathoracic tumor burden, or other factors need to be defined.
Clinicians need predictive biomarkers for ICI-related pneumonitis (e.g., in peripheral blood, pulmonary function testing, or bronchoscopy specimens). At-risk patients may benefit from early intervention.
The limitations of single-institution record reviews in guiding real-world patient management notwithstanding, these reviews illustrate the value of registries and prospective studies to guide the path forward. Taking these next steps will ensure for our patients that the success of immune-targeted therapy against their cancer never becomes a Pyrrhic victory.
The Johns Hopkins investigators and the editorialists reported having no disclosures. The Memorial Sloan Kettering investigators disclosed relationships with Targeted Oncology, Merck, Array BioPharma, Novartis, and many other companies.
Dr. Lyss was a community-based medical oncologist and clinical researcher for more than 35 years before his recent retirement. His clinical and research interests were focused on breast and lung cancers, as well as expanding clinical trial access to medically underserved populations. He is based in St. Louis. He has no conflicts of interest.
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.