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Cross-training across the map
There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.
Here, in my little three-person office, the only thing my staff can’t do is see patients.
Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.
So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.
At this time, I’ve not only gotten used to it, but really don’t mind it.
We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.
Nobody worries about what to throw together for dinner if they get home late.
It saves money on rent, and money and time on transportation.
Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.
Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.
My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.
When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.
I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.
Here, in my little three-person office, the only thing my staff can’t do is see patients.
Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.
So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.
At this time, I’ve not only gotten used to it, but really don’t mind it.
We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.
Nobody worries about what to throw together for dinner if they get home late.
It saves money on rent, and money and time on transportation.
Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.
Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.
My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.
When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.
I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.
Here, in my little three-person office, the only thing my staff can’t do is see patients.
Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.
So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.
At this time, I’ve not only gotten used to it, but really don’t mind it.
We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.
Nobody worries about what to throw together for dinner if they get home late.
It saves money on rent, and money and time on transportation.
Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.
Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.
My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.
When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.
I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.
Dr. Block has a solo neurology practice in Scottsdale, Ariz.
Topical gene therapy for dystrophic epidermolysis bullosa shows promise
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
INDIANAPOLIS – An investigational compared with placebo, according to results from a small phase 3 study.
DEB is a serious, ultra-rare genetic blistering disease caused by mutations in the COL7A1 gene, encoding for type VII collagen and leading to skin fragility and wounds. No approved therapies are currently available. In the study, treatment was generally well tolerated.
“B-VEC is the first treatment that has not only been shown to be effective, but the first to directly target the defect through topical application,” the study’s principal investigator, Shireen V. Guide, MD, said in an interview during a poster session at the annual meeting of the Society for Pediatric Dermatology. “It delivers type VII collagen gene therapy to these patients, which allows healing in areas that they may have had open since birth. It’s been life-changing for them.”
B-VEC is a herpes simplex virus (HSV-1)-based topical, redosable gene therapy being developed by Krystal Biotech that is designed to restore functional COL7 protein by delivering the COL7A1 gene. For the phase 3, multicenter, double-blind, placebo-controlled study known GEM-3, Dr. Guide, who practices dermatology in Rancho Santa Margarita, Calif., and her colleagues, including Peter Marinkovich, MD, from Stanford (Calif.) University, and Mercedes Gonzalez, MD, from the University of Miami, enrolled 31 patients aged 6 months and older with genetically confirmed DEB. Each patient had one wound treated randomized 1:1 to treatment with B-VEC once a week or placebo for 6 months. The mean age of the 31 study participants was 17 years, 65% were male, 65% were White, and 19% were Asian.
The primary endpoint was complete wound healing (defined as 100% wound closure from exact wound area at baseline, specified as skin re-epithelialization without drainage) at 6 months. Additional endpoints included complete wound healing at 3 months and change in pain associated with wound dressing changes.
At 3 months, 70% of wounds treated with B-VEC met the endpoint of complete wound healing, compared with 20% of wounds treated with placebo (P < .005). At 6 months, 67% of wounds treated with B-VEC met the endpoint of complete wound healing compared with 22% of those treated with placebo (P < .005).
Of the total wounds that closed at 3 months, 67% of wounds treated with B-VEC were also closed at 6 months, compared with 33% of those treated with placebo (P = .02). In other findings, a trend toward decreased pain was observed in wounds treated with B-VEC vs. those treated with placebo.
B-VEC was well tolerated with no treatment-related serious adverse events or discontinuations. Three patients experienced a total of five serious adverse events during the study: anemia (two events), and cellulitis, diarrhea, and positive blood culture (one event each). None were considered related to the study drug.
Dr. Guide, who is on staff at Children’s Health of Orange County, Orange, Calif., characterized B-VEC as “very novel because it’s very practical.”
To date, all treatments for DEB “have been extremely labor intensive, including skin grafting and hospitalizations. It’s a topical application that can be done in the office and potentially applied at home in the future. It’s also durable. Not only are the [treated] areas closing, but they are staying closed.”
Kalyani S. Marathe, MD, MPH, director of the dermatology division at Cincinnati Children’s Hospital, who was asked to comment on the study, said that topical application of B-VEC “allows the side effect profile to be very favorable. The results are remarkable in the amount of wound healing and reduction in pain.”
The tolerability of this medication “is crucial,” she added. “EB patients have a lot of pain from their wounds and so any treatment needs to be as painless as possible for it to be usable. I’m very excited about the next phase of studies for this medication and hopeful that it heralds new treatments for our EB patients.”
In June 2022, the manufacturer announced that it had submitted a biologics license application to the Food and Drug Administration for approval of B-VEC for the treatment of DEB, and that it anticipates submitting an application for marketing authorization with the European Medical Agency (EMA) in the second half of 2022.
Dr. Guide disclosed that she has served as an investigator for Krystal Biotech, Innovaderm Research, Arcutis, Premier Research, Paidion, and Castle Biosciences. Dr. Marathe disclosed that she has served as an adviser for Verrica, and that Cincinnati Children’s Hospital is a site for the next phase studies for B-VEC.
*This story was updated on July 25.
AT SPD 2022
‘Stunning variation’ in CV test, procedure costs revealed at top U.S. hospitals
Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.
The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.
“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.
“For example, there was a 10-fold difference in the median price of an echocardiogram, and these differences were even larger for common procedures” such as percutaneous coronary intervention (PCI) and pacemaker implantation, he said. “It’s hard to argue that this variation reflects quality of care, given that we looked at a top group of highly ranked hospitals.”
“Even more striking was how the price of a cardiovascular test within the very same hospital could differ across commercial insurance companies,” he said. “For example, the price of a stress test varied 5-fold in one hospital, and in another hospital, more than 4-fold for a coronary angiogram.”
Dr. Wadhera is senior author on the study published online as a research letter in JAMA Internal Medicine, with lead author Andrew S. Oseran, MD, MBA, also from Beth Israel Deaconess Medical Center.
Difficulties with data, interpretation
The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.
Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.
“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”
Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.
The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.
A similar pattern was seen for self-pay cash prices.
Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.
The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
‘More needed besides transparency’
“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.
That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”
Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”
Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”
“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”
Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.
A version of this article first appeared on Medscape.com.
Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.
The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.
“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.
“For example, there was a 10-fold difference in the median price of an echocardiogram, and these differences were even larger for common procedures” such as percutaneous coronary intervention (PCI) and pacemaker implantation, he said. “It’s hard to argue that this variation reflects quality of care, given that we looked at a top group of highly ranked hospitals.”
“Even more striking was how the price of a cardiovascular test within the very same hospital could differ across commercial insurance companies,” he said. “For example, the price of a stress test varied 5-fold in one hospital, and in another hospital, more than 4-fold for a coronary angiogram.”
Dr. Wadhera is senior author on the study published online as a research letter in JAMA Internal Medicine, with lead author Andrew S. Oseran, MD, MBA, also from Beth Israel Deaconess Medical Center.
Difficulties with data, interpretation
The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.
Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.
“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”
Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.
The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.
A similar pattern was seen for self-pay cash prices.
Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.
The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
‘More needed besides transparency’
“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.
That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”
Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”
Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”
“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”
Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.
A version of this article first appeared on Medscape.com.
Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.
The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.
“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.
“For example, there was a 10-fold difference in the median price of an echocardiogram, and these differences were even larger for common procedures” such as percutaneous coronary intervention (PCI) and pacemaker implantation, he said. “It’s hard to argue that this variation reflects quality of care, given that we looked at a top group of highly ranked hospitals.”
“Even more striking was how the price of a cardiovascular test within the very same hospital could differ across commercial insurance companies,” he said. “For example, the price of a stress test varied 5-fold in one hospital, and in another hospital, more than 4-fold for a coronary angiogram.”
Dr. Wadhera is senior author on the study published online as a research letter in JAMA Internal Medicine, with lead author Andrew S. Oseran, MD, MBA, also from Beth Israel Deaconess Medical Center.
Difficulties with data, interpretation
The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.
Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.
“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”
Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.
The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.
A similar pattern was seen for self-pay cash prices.
Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.
The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
‘More needed besides transparency’
“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.
That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”
Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”
Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”
“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”
Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.
A version of this article first appeared on Medscape.com.
Neuroscientist alleges irregularities in Alzheimer’s research
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.
Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.
to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.
“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.
In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.
Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
High stakes
Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.
“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.
However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”
Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.
Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.
This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.
However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
A matter of trust
Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”
Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”
The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.
Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.
“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.
Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center.
A version of this article first appeared on Medscape.com.
Immune response may explain brain damage after COVID-19
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
Should monkeypox be considered an STD? Experts debate
As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.
Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.
But health experts say that doesn’t make it an STD – at least not in “the classic sense.”
“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.
He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.
Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.
“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those –
But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.
“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.
“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”
Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.
“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”
One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.
Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.
In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.
A version of this article first appeared on WebMD.com.
As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.
Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.
But health experts say that doesn’t make it an STD – at least not in “the classic sense.”
“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.
He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.
Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.
“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those –
But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.
“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.
“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”
Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.
“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”
One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.
Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.
In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.
A version of this article first appeared on WebMD.com.
As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.
Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.
But health experts say that doesn’t make it an STD – at least not in “the classic sense.”
“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.
He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.
Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.
“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those –
But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.
“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.
“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”
Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.
“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”
One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.
Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.
In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.
A version of this article first appeared on WebMD.com.
Study pinpoints best predictor of when reflux symptoms don’t require PPI
Four days is an optimal time for wireless reflux monitoring to determine which patients can stop taking proton pump inhibitors (PPIs) and which ones need long-term antireflux therapy, researchers report.
“This first-of-its kind double-blinded clinical trial demonstrates the comparable, and in some cases better, performance of a simple assessment of daily acid exposure from multiple days of recording compared to other composite or complex assessments,” write Rena Yadlapati, MD, with the Division of Gastroenterology at the University of California, San Diego, and her coauthors.
Their findings were published online in the American Journal of Gastroenterology.
A substantial percentage of patients who have esophageal reflux symptoms do not have gastroesophageal reflux disease (GERD) and can stop taking PPIs.
Wireless reflux monitoring performed while patients are not taking PPIs is the gold standard for determining whether a patient has abnormal acid from GERD, but the optimal daily acid exposure time (AET) and the optimal duration of monitoring have not been well studied.
Aiming to fill this knowledge gap, Dr. Yadlapati and her colleagues conducted a single-arm, double-blinded clinical trial over 4 years at two tertiary care centers. They enrolled adult patients who had demonstrated an inadequate response to more than 8 weeks’ treatment with PPIs.
Study participants were asked to stop taking their PPI for 3 weeks in order for the investigators to determine the rate of relapse after PPI use and establish the study reference standard to discontinue therapy. During the 3-week period, after having stopped taking PPIs for at least a week, patients underwent 96-hour wireless reflux monitoring. They were then told to continue not taking PPIs for an additional 2 weeks. They could use over-the-counter antacids for symptom relief.
The primary outcome was whether PPIs could be successfully discontinued or restarted within 3 weeks. Of the 132 patients, 30% were able to stop taking PPIs.
AET less than 4.0% best discontinuation predictor
The team came to two key conclusions.
They found that acid exposure time of less than 4.0% was the best predictor of when stopping PPIs will be effective without worsening symptoms (odds ratio, 2.9; 95% confidence interval, 1.4-6.4). Comparatively, 45% (22 of 49 patients) with total AET of 4.0% or less discontinued taking PPIs, versus 22% (18 of 83 patients) with total AET of more than 4.0%.
Additionally, the investigators concluded that 96 hours of monitoring was better than 48 hours or fewer in predicting whether patients could stop taking PPIs (area under curve [AUC] for 96 hours, 0.63, versus AUC for 48 hours, 0.57).
Dr. Yadlapati told this news organization that the findings should be practice-changing.
“You really need to test for 4 days,” she said. She noted that the battery life of the monitor is 96 hours, and clinicians commonly only test for 2 days.
With only 1-2 days of monitoring, there is too much variability in how much acid is in the esophagus from one day to another. Monitoring over a 4-day period gives a clearer picture of acid exposure burden, she said.
Her advice: “If you have a patient with heartburn or chest pain and you think it might be from reflux, and they’re not responding to a trial of PPI, get the reflux monitoring. Don’t wait.”
After 4 days of monitoring, if exposure to acid is low, “they should really be taken off their PPI therapy,” she said.
They likely have a condition that requires a different therapy, she added.
“It is very consistent with what we have thought to be the case and what some lower-quality studies have shown,” she said. “It just hadn’t been done in a clinical trial with a large patient population and with a full outcome.”
PPI often used inappropriately
Interest is high both in discontinuing PPI in light of widespread and often inappropriate use and in not starting treatment with PPIs for patients who need a different therapy.
As this news organization has reported, some studies have linked long-term PPI use with intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, vitamin deficiencies, heart attacks, strokes, dementia, and early death.
Avin Aggarwal, MD, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona, Tucson, said in an interview that this study provides the evidence needed to push for practice change.
He said his center has been using 48-hour reflux monitoring. He said that anecdotally, they had gotten better data with 4-day monitoring, but evidence was not directly tied to a measurable outcome such as this study provides.
With 4-day monitoring, “we get way more symptoms on the recorder to actually correlate them with reflux or not,” he said.
He said he will now push for the 96-hour monitoring in his clinic.
He added that part of the problem is in assuming patients have GERD and initiating PPIs in the first place without a specific diagnosis of acid reflux.
Patients, he said, are often aware of the long-term side effects of PPIs and are approaching their physicians to see whether they can discontinue them.
The data from this study, he said, will help guide physicians on when it is appropriate to discontinue treatment.
Dr. Yadlapati is a consultant for Medtronic, Phathom Pharmaceuticals, and StatLinkMD and receives research support from Ironwood Pharmaceuticals. She is on the advisory board with stock options for RJS Mediagnostix. Other study coauthors report ties to Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles, Johnson & Johnson, Reckitt, Phathom Pharmaceuticals, Daewood, Takeda, and Crospon. Study coauthor Michael F. Vaezi, MD, PHD, holds a patent on mucosal integrity by Vanderbilt. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Four days is an optimal time for wireless reflux monitoring to determine which patients can stop taking proton pump inhibitors (PPIs) and which ones need long-term antireflux therapy, researchers report.
“This first-of-its kind double-blinded clinical trial demonstrates the comparable, and in some cases better, performance of a simple assessment of daily acid exposure from multiple days of recording compared to other composite or complex assessments,” write Rena Yadlapati, MD, with the Division of Gastroenterology at the University of California, San Diego, and her coauthors.
Their findings were published online in the American Journal of Gastroenterology.
A substantial percentage of patients who have esophageal reflux symptoms do not have gastroesophageal reflux disease (GERD) and can stop taking PPIs.
Wireless reflux monitoring performed while patients are not taking PPIs is the gold standard for determining whether a patient has abnormal acid from GERD, but the optimal daily acid exposure time (AET) and the optimal duration of monitoring have not been well studied.
Aiming to fill this knowledge gap, Dr. Yadlapati and her colleagues conducted a single-arm, double-blinded clinical trial over 4 years at two tertiary care centers. They enrolled adult patients who had demonstrated an inadequate response to more than 8 weeks’ treatment with PPIs.
Study participants were asked to stop taking their PPI for 3 weeks in order for the investigators to determine the rate of relapse after PPI use and establish the study reference standard to discontinue therapy. During the 3-week period, after having stopped taking PPIs for at least a week, patients underwent 96-hour wireless reflux monitoring. They were then told to continue not taking PPIs for an additional 2 weeks. They could use over-the-counter antacids for symptom relief.
The primary outcome was whether PPIs could be successfully discontinued or restarted within 3 weeks. Of the 132 patients, 30% were able to stop taking PPIs.
AET less than 4.0% best discontinuation predictor
The team came to two key conclusions.
They found that acid exposure time of less than 4.0% was the best predictor of when stopping PPIs will be effective without worsening symptoms (odds ratio, 2.9; 95% confidence interval, 1.4-6.4). Comparatively, 45% (22 of 49 patients) with total AET of 4.0% or less discontinued taking PPIs, versus 22% (18 of 83 patients) with total AET of more than 4.0%.
Additionally, the investigators concluded that 96 hours of monitoring was better than 48 hours or fewer in predicting whether patients could stop taking PPIs (area under curve [AUC] for 96 hours, 0.63, versus AUC for 48 hours, 0.57).
Dr. Yadlapati told this news organization that the findings should be practice-changing.
“You really need to test for 4 days,” she said. She noted that the battery life of the monitor is 96 hours, and clinicians commonly only test for 2 days.
With only 1-2 days of monitoring, there is too much variability in how much acid is in the esophagus from one day to another. Monitoring over a 4-day period gives a clearer picture of acid exposure burden, she said.
Her advice: “If you have a patient with heartburn or chest pain and you think it might be from reflux, and they’re not responding to a trial of PPI, get the reflux monitoring. Don’t wait.”
After 4 days of monitoring, if exposure to acid is low, “they should really be taken off their PPI therapy,” she said.
They likely have a condition that requires a different therapy, she added.
“It is very consistent with what we have thought to be the case and what some lower-quality studies have shown,” she said. “It just hadn’t been done in a clinical trial with a large patient population and with a full outcome.”
PPI often used inappropriately
Interest is high both in discontinuing PPI in light of widespread and often inappropriate use and in not starting treatment with PPIs for patients who need a different therapy.
As this news organization has reported, some studies have linked long-term PPI use with intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, vitamin deficiencies, heart attacks, strokes, dementia, and early death.
Avin Aggarwal, MD, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona, Tucson, said in an interview that this study provides the evidence needed to push for practice change.
He said his center has been using 48-hour reflux monitoring. He said that anecdotally, they had gotten better data with 4-day monitoring, but evidence was not directly tied to a measurable outcome such as this study provides.
With 4-day monitoring, “we get way more symptoms on the recorder to actually correlate them with reflux or not,” he said.
He said he will now push for the 96-hour monitoring in his clinic.
He added that part of the problem is in assuming patients have GERD and initiating PPIs in the first place without a specific diagnosis of acid reflux.
Patients, he said, are often aware of the long-term side effects of PPIs and are approaching their physicians to see whether they can discontinue them.
The data from this study, he said, will help guide physicians on when it is appropriate to discontinue treatment.
Dr. Yadlapati is a consultant for Medtronic, Phathom Pharmaceuticals, and StatLinkMD and receives research support from Ironwood Pharmaceuticals. She is on the advisory board with stock options for RJS Mediagnostix. Other study coauthors report ties to Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles, Johnson & Johnson, Reckitt, Phathom Pharmaceuticals, Daewood, Takeda, and Crospon. Study coauthor Michael F. Vaezi, MD, PHD, holds a patent on mucosal integrity by Vanderbilt. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Four days is an optimal time for wireless reflux monitoring to determine which patients can stop taking proton pump inhibitors (PPIs) and which ones need long-term antireflux therapy, researchers report.
“This first-of-its kind double-blinded clinical trial demonstrates the comparable, and in some cases better, performance of a simple assessment of daily acid exposure from multiple days of recording compared to other composite or complex assessments,” write Rena Yadlapati, MD, with the Division of Gastroenterology at the University of California, San Diego, and her coauthors.
Their findings were published online in the American Journal of Gastroenterology.
A substantial percentage of patients who have esophageal reflux symptoms do not have gastroesophageal reflux disease (GERD) and can stop taking PPIs.
Wireless reflux monitoring performed while patients are not taking PPIs is the gold standard for determining whether a patient has abnormal acid from GERD, but the optimal daily acid exposure time (AET) and the optimal duration of monitoring have not been well studied.
Aiming to fill this knowledge gap, Dr. Yadlapati and her colleagues conducted a single-arm, double-blinded clinical trial over 4 years at two tertiary care centers. They enrolled adult patients who had demonstrated an inadequate response to more than 8 weeks’ treatment with PPIs.
Study participants were asked to stop taking their PPI for 3 weeks in order for the investigators to determine the rate of relapse after PPI use and establish the study reference standard to discontinue therapy. During the 3-week period, after having stopped taking PPIs for at least a week, patients underwent 96-hour wireless reflux monitoring. They were then told to continue not taking PPIs for an additional 2 weeks. They could use over-the-counter antacids for symptom relief.
The primary outcome was whether PPIs could be successfully discontinued or restarted within 3 weeks. Of the 132 patients, 30% were able to stop taking PPIs.
AET less than 4.0% best discontinuation predictor
The team came to two key conclusions.
They found that acid exposure time of less than 4.0% was the best predictor of when stopping PPIs will be effective without worsening symptoms (odds ratio, 2.9; 95% confidence interval, 1.4-6.4). Comparatively, 45% (22 of 49 patients) with total AET of 4.0% or less discontinued taking PPIs, versus 22% (18 of 83 patients) with total AET of more than 4.0%.
Additionally, the investigators concluded that 96 hours of monitoring was better than 48 hours or fewer in predicting whether patients could stop taking PPIs (area under curve [AUC] for 96 hours, 0.63, versus AUC for 48 hours, 0.57).
Dr. Yadlapati told this news organization that the findings should be practice-changing.
“You really need to test for 4 days,” she said. She noted that the battery life of the monitor is 96 hours, and clinicians commonly only test for 2 days.
With only 1-2 days of monitoring, there is too much variability in how much acid is in the esophagus from one day to another. Monitoring over a 4-day period gives a clearer picture of acid exposure burden, she said.
Her advice: “If you have a patient with heartburn or chest pain and you think it might be from reflux, and they’re not responding to a trial of PPI, get the reflux monitoring. Don’t wait.”
After 4 days of monitoring, if exposure to acid is low, “they should really be taken off their PPI therapy,” she said.
They likely have a condition that requires a different therapy, she added.
“It is very consistent with what we have thought to be the case and what some lower-quality studies have shown,” she said. “It just hadn’t been done in a clinical trial with a large patient population and with a full outcome.”
PPI often used inappropriately
Interest is high both in discontinuing PPI in light of widespread and often inappropriate use and in not starting treatment with PPIs for patients who need a different therapy.
As this news organization has reported, some studies have linked long-term PPI use with intestinal infections, pneumonia, stomach cancer, osteoporosis-related bone fractures, chronic kidney disease, vitamin deficiencies, heart attacks, strokes, dementia, and early death.
Avin Aggarwal, MD, a gastroenterologist and medical director of Banner Health’s South Campus endoscopy services and clinical assistant professor at the University of Arizona, Tucson, said in an interview that this study provides the evidence needed to push for practice change.
He said his center has been using 48-hour reflux monitoring. He said that anecdotally, they had gotten better data with 4-day monitoring, but evidence was not directly tied to a measurable outcome such as this study provides.
With 4-day monitoring, “we get way more symptoms on the recorder to actually correlate them with reflux or not,” he said.
He said he will now push for the 96-hour monitoring in his clinic.
He added that part of the problem is in assuming patients have GERD and initiating PPIs in the first place without a specific diagnosis of acid reflux.
Patients, he said, are often aware of the long-term side effects of PPIs and are approaching their physicians to see whether they can discontinue them.
The data from this study, he said, will help guide physicians on when it is appropriate to discontinue treatment.
Dr. Yadlapati is a consultant for Medtronic, Phathom Pharmaceuticals, and StatLinkMD and receives research support from Ironwood Pharmaceuticals. She is on the advisory board with stock options for RJS Mediagnostix. Other study coauthors report ties to Medtronic, Diversatek, Ironwood, Iso-Thrive, Quintiles, Johnson & Johnson, Reckitt, Phathom Pharmaceuticals, Daewood, Takeda, and Crospon. Study coauthor Michael F. Vaezi, MD, PHD, holds a patent on mucosal integrity by Vanderbilt. Dr. Aggarwal reports no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Prior decompensation in alcohol-associated hepatitis not an ‘absolute contraindication’ for early liver transplant
Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.
Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.
In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.
However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
Not all bad news
The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.
There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.
Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).
However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”
Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.
“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
A note of caution for early LT
About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.
“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.
He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.
Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.
The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.
Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.
Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.
In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.
However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
Not all bad news
The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.
There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.
Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).
However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”
Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.
“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
A note of caution for early LT
About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.
“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.
He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.
Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.
The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.
Past decompensation in alcohol-associated hepatitis may be linked with worse survival following liver transplantation, but it’s not all bad news, according to a retrospective study.
Traditionally, patients with alcoholic liver disease were asked to be alcohol free for 6 months before consideration for a liver transplantation. In recent years, there’s been a loosening of that policy, with physicians considering “early” liver transplantation (early LT) instead of waiting 6 months. “It became obvious that a lot of patients do resume alcohol use after transplant, and most of them don’t appear to suffer too much in the way of adverse consequences,” said Paul Martin, MD, chief of hepatology at the University of Miami, who was not involved in the current research.
In 2011, a study confirmed that suspicion, finding that 6-month survival was 77% among carefully selected patients with alcohol-associated hepatitis for whom the 6-month sobriety requirement was waived; 6-month survival in those who did not receive a transplant was 22%. The selection criteria included the presence of supportive family members, the absence of severe coexisting conditions, and a commitment to abstaining from alcohol.
However, authors of the current study, published in the American Journal of Gastroenterology sought nuance: The appropriateness of prior decompensation as exclusion criteria in published studies is unknown, so the researchers compared outcomes of patients with prior versus first-time liver decompensation in alcohol-associated hepatitis.
Not all bad news
The study included 241 patients from six sites who consecutively received early LT between 2007 and 2020. Among these, 210 were identified as having a first-time liver decompensation event and 31 as having had a prior history of liver decompensation, defined as being diagnosed with ascites, hepatic encephalopathy, variceal bleeding, or jaundice.
There was no significant difference in median age, Model for End-Stage Liver Disease (MELD) scores, or post–liver transplant follow-up time between those with first-time liver decompensation or a prior history. The unadjusted 1-year survival rate was 93% in the first decompensation group (95% confidence interval, 89%-96%) and 86% in the prior decompensation group (95% CI, 66%-94%). The unadjusted 3-year survival rates were 85% (95% CI, 79%-90%) and 78% (95% CI, 57%-89%), respectively.
Importantly, the researchers found an association between prior decompensation and higher adjusted post–liver transplantation mortality (adjusted hazard ratio, 2.72; 95% CI, 1.61-4.59) and harmful alcohol use (aHR, 1.77; 95% CI, 1.07-2.92).
However, the researchers noted that these patients, who had MELD scores of 39 and previous decompensation, were at exceptionally high risk of short-term mortality, but still had 1- and 3-year survival rates above 85% and 75%, respectively, with early LT. “While longer follow-up is desirable as graft failure related to alcohol is most apparent after 5-years post LT, these results suggest that prior decompensation alone should not be considered an absolute contraindication to early LT.”
Limitations of the study included its retrospective data and small sample size for patients with prior decompensation.
“These findings validate the value of the ‘first decompensation’ criteria in published experiences regarding early LT for [alcoholic hepatitis],” the investigators concluded. “Further larger and prospective studies with longer-term follow-up will be needed to assess ways to optimally select patients in this cohort who may benefit most from early LT, and ways to manage patients at highest risk for worse outcomes post LT.”
A note of caution for early LT
About half of all liver mortality is attributable to alcoholic-associated liver disease. Corticosteroids can improve short-term survival, but there are no medications proven to increase long-term survival. That leaves liver transplant as the sole alternative for patients who don’t respond to corticosteroids.
“Programs in North America have liberalized their acceptance criteria for patients with alcoholic liver disease, and that’s resulted in large numbers of patients being transplanted who have less than 6 months abstinence. And overall, the results seem good, but I think this paper strikes an appropriate note of caution. In essence, if a patient had at least one prior episode of liver failure related to alcoholic excess and had recovered from that, and continued to drink and got into trouble again, [and then] presented for consideration for liver transplantation, the fact that they resumed alcohol use after prior episodes of decompensation suggests that they may be less-than-ideal candidates [for liver transplantation],” said Dr. Martin.
He pointed out important caveats to the study, including its retrospective nature and its inclusion of a relatively small number of patients with a history of liver decompensation. But it reinforces what physicians generally know, which is that some patients with severe alcohol use disorder also have liver failure, and they tend to fare worse than others after a liver transplant.
Still, physicians also face a conundrum because there are increasing numbers of younger patients who won’t survive if they don’t get a liver transplant. “The challenge is picking out patients who are going to be good candidates from a purely medical point of view, but have a low likelihood of resuming alcohol use after transplantation [which could injure] the new liver,” said Dr. Martin. The new study has the potential to provide some additional guidance in patient selection.
The study authors disclosed no relevant conflicts of interest. Dr. Martin has no relevant financial disclosures.
FROM THE AMERICAN JOURNAL OF GASTROENTEROLOGY
The Team Approach to Managing Type 2 Diabetes
Those of us who treat patients with type 2 diabetes (T2D) daily have long recognized a disturbing irony: diabetes is a disease whose management requires consistency in approach and constancy in delivery, but it is most prevalent among those whose lives often allow little to no time for either.
In our clinic, many patients with diabetes are struggling, in some way, to incorporate diabetes management into their daily lives. They are juggling multiple jobs and family responsibilities; they are working jobs with inconsistent access to food or refrigeration (such as farming, service industry work, and others); and many—even those with insurance—are struggling to afford their insulin and non insulin medications, insulin administration supplies, and glucose testing equipment.
Studies show how stress deleteriously affects this disease. The body does not deal well with these frequent and persistent stressors; higher cortisol levels result in higher blood glucose levels, increased systemic inflammation, and other drivers of both diabetes and its complications; all have been extensively documented.
What has been frustrating for our clinical community is knowing that since the early 2000s, new diabetes medications and technologies have been available that can make a difference in our patients’ lives, but for various reasons, they have not been well adopted, particularly among patients most likely to benefit from them. Consequently, we have not consistently seen meaningfully reduced glycated hemoglobin (A1c) levels or reduced rates of acute or chronic diabetes complications. Therapeutic inertia exists at the patient, systemic, and physician levels.
Many of the new glucose-lowering medications can also improve cardiovascular and kidney disease outcomes with low risk for hypoglycemia and weight gain. Diabetes technologies like insulin pumps and continuous glucose monitors (CGM) have been demonstrated in clinical trials to improve A1c and reduce hypoglycemia risk. But the reality is that clinicians are seeing an increasing number of patients with high A1c, with hypoglycemia, with severe hyperglycemia, and with long-term diabetes complications.
If these advancements are supposed to improve health outcomes, why are patient, community, and population health not improving? Why are some patients not receiving the care they need, while others get extra services that do not improve their health and may even harm them?
These advancements also create new questions for clinicians. At what point in the disease course should existing medications be ramped up, ramped down, or changed? Which patient characteristics or comorbidities allow or do not allow these changes? When should we use technologies or when does their burden outweigh their potential benefits? What resources and support systems do our patients need to live well with their disease and how can these be procured?
Herein lies the problem: Diabetes is a dynamic disease that needs to be handled in a dynamic way, and that has not universally—or even frequently—occurred. Management must be a team endeavor, meaning that both patient and clinician must be proactive in diabetes management. It has been our experience, demonstrated in our work and in other studies, that success relies on a robust and comprehensive primary care system whose team members—physicians, advanced practice providers, nurses, pharmacists, certified diabetes care and education specialists, social workers, nurses, pharmacists, and dietitians—are all resilient and motivated to tackle one of the most complex, multifaceted, and multidimensional chronic health conditions in our practice.
Proactivity also includes consistent monitoring, learning from successes and failures, and public reporting. For the patient, proactive involvement generally means self-care multiple times a day.
Let us now discuss the evidence that prompted our team’s proactive approach to caring for people living with diabetes.
Gauges and perspective
The prevalence of T2D in this country stands at 11.3% within the adult population. Between 2015 and 2020, death from diabetes increased by 27%.
For years, the research community has documented the wide range of socioeconomic factors that increase the risk for developing T2D and that, once developed, make it more difficult for patients to manage their disease and achieve optimal health outcomes that are possible with available medications and technologies.
In 2019, Kazemian et al published work that examined the indicators of diabetes management progress (eg, A1c levels, cholesterol levels) of 1742 individuals, from 2005 to 2016. Just 23% to 25% of these patients achieved all goals, even though, during the study period, numerous medications were approved to manage disease better. Arguably, these should have improved the all-goal findings in the study.
The first injectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) was approved in 2005; between 2013 and 2016, the FDA also approved 4 sodium-glucose cotransporter 2 (SGLT2) inhibitors. Both medication classes can safely and effectively lower A1c with no weight gain and low risk for hypoglycemia. Over the past 4 years, a robust body of evidence has emerged to show that GLP-1 RAs and SGLT2 inhibitors not only lower A1c, but also reduce the likelihood of death from cardiovascular and kidney diseases. SGLT2 inhibitors are better at saving lives from hypertensive heart failure while the GLP-1 RAs are more protective from atherosclerotic cardiovascular events like myocardial infarction and stroke, as compared with placebo. Yet, these medications have not been, and continue not to be, regularly prescribed. In 1 study, the authors found that the rate of use for SGLT2 inhibitors was 3.8% in 2015 and 11.9% in 2019.
But there are several other reasons that patients do not receive these medicines.
Insurance
We conducted a retrospective cohort study of 382,574 adults between 58 and 66 years of age, insured by either a Medicare Advantage plan or commercial insurance, and compared treatment initiation of the 3 most common brand-name, second-line diabetes medications (as opposed to generic sulfonylureas), between 2016 and 2019. The rate of initiation was universally lower for Medicare Advantage members vs commercially insured individuals.
While the rates of initiation of GLP-1 RAs, SGLT2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors increased between 2016 and 2019, rates were significantly higher among patients with commercial insurance. Specifically, GLP-1 RA initiation increased from 2.1% to 20.0% among commercial insurance beneficiaries and from 1.5% to 11.4% among Medicare Advantage beneficiaries. SGLT2 inhibitor initiation increased from 2.7% to 18.2% with commercial insurance and from 1.57% to 8.51% with Medicare Advantage. DPP-4 inhibitor initiation increased from 3.3% to 11.7% with commercial insurance and from 2.44% to 7.68% with Medicare Advantage. Within each calendar year, the odds of initiating one of these 3 medications with Medicare Advantage as compared with commercial insurance ranged from 0.28 to 0.70 for GLP-1 RAs; from 0.21 to 0.57 for SGLT2 inhibitors; and from 0.37 to 0.73 for DPP-4 inhibitors.
We also looked at the initiation of these medications in individuals with cardiorenal comorbidities. In many cases, a drug was prescribed indiscriminately. A patient who would benefit from a GLP-1 RA because of cardiovascular, cerebrovascular, or kidney disease was less likely to be prescribed a GLP-1 RA than a medication like a DPP-4 inhibitor, which usually has the same formulary tier/class but does not have any of the cardiovascular or kidney benefits. Likewise, in those with heart failure or kidney disease, an SGLT2 inhibitor would have been the appropriate choice, but these patients were too often started on a DPP-4 inhibitor, which is not advised for those with heart failure and does provide kidney benefits.
Last year, Tummalapalli et al, in their evaluation of 4135 US health plans, including commercial- or employer-based, Medicare, Medicaid, and other public health plans, identified multiple barriers to accessing SGLT2 inhibitor medications. While all plans included at least 1 SGLT2 inhibitor on their formularies, they restricted access in other ways. Prior authorizations were required by nearly half of Medicaid plans and nearly 40% of other public plans such as the Veterans Health Administration. Medicare and other public plans commonly imposed quantity limits on fills. Commercial plans frequently (up to 40%) required step therapy (use or failure of a generic diabetes medication) before approval. Copayments were also high in commercial plans, Medicare, and others.
The need for prior authorizations dominates attempts to prescribe. Centene Corporation, for example, which manages plans for private and public payers, will not approve use of an SGLT2 inhibitor until the patient fails for 3 consecutive months on a prior treatment, has established cardiovascular disease or diabetic nephropathy, or has multiple cardiovascular risk factors. These comorbidities must be documented and verified, and the prior authorizations must be completed, often resulting in substantial administrative burden to clinicians. No wonder many, especially in primary care, may be wary of prescribing drugs that come with a paperwork trail and hours spent on documentation and insurance appeals, rather than on patient care.
The same can be said for prescribing a GLP-1 RA. United Healthcare’s Oxford Benefit Management requires that clinicians show a “history of suboptimal response, contraindication, or intolerance to metformin” before prescribing any of the 8 GLP-1 RAs.
The average retail cost of 30 empagliflozin tablets, a once-daily medication, is $752. During the pandemic, 24% of the 5000 patients surveyed in an American Diabetes Association (ADA) poll used their stimulus check, relied on loans, or spent savings to pay for diabetes care. GLP-1 RA medications are even more expensive. Depending on the patient’s pharmacy benefits, they may have to pay a substantial coinsurance out of pocket even after the annual deductible is met, creating financial barriers to starting and continuing recommended, evidence-based medications. Even if patients do get the recommended medications, they may be forced to ration other aspects of their lives, including other medications, food, and other necessities.
There are other important barriers to optimal utilization of evidence-based therapies, stemming from the fundamental social determinants of health: low income, low education level, and living in a socioeconomically deprived neighborhood.
Social Determinants of Health
Diabetes prevalence is higher in patients experiencing socioeconomic and other structural barriers to health and health care. Fundamentally, 1 study showed that prevalence of diabetes was 1.4 times higher among people living on less than $15,000 a year, as opposed to those earning at least $50,000 a year.
The risk of diabetes complications is also higher in individuals experiencing food or housing insecurity, those who have low income or education level, and residents in rural and socioeconomically deprived neighborhoods. Importantly, the same patient populations are also less likely to receive timely evidence-based care, contributing to and worsening health disparities. Despite their prevalence and importance, social determinants of health (SDoH) are not routinely recognized or discussed during clinical encounters, such that improving diabetes care and health outcomes is predicated on developing a system to screen for, recognize, and address the wide range of barriers faced by our patients. If a patient cannot afford a new medication or get to the clinic on a regular basis, lacks access to healthy food, or does not have time for diabetes self-management education or to focus on their health, then their well-being will suffer.
Many of these SDoH disproportionately affect racial and ethnic minority populations as the direct result of longstanding and deeply embedded systems, policies, and laws that underlie disparities in diabetes incidence, prevalence, management, and outcomes. As such, structural racism is increasingly recognized as a root cause of health disparities in diabetes and other chronic health conditions.
Proactive strategies
Since reactive care has not and cannot provide patients with the help they need and deserve, many in the diabetes care community have turned to proactive, team-based care. The Chronic Care Model, established in the 1990s, stresses decision-making support, strong team organization and delivery system design, and the wherewithal to monitor progress continually. Research has shown that the best results for patients stem from a multidisciplinary, data-driven, and proactive approach to identifying and meeting the totality of patient care needs.
The ADA stresses the importance of comprehensive, team-based care for successful management of diabetes. This includes expanding the role of teams to implement evidence-based diabetes care, using electronic health record tools to support timely and guideline-recommended delivery of services, empowering and educating patients and caregivers, eliciting and addressing financial and psychosocial barriers to care, and identifying, developing, and engaging community resources to support better health and well-being.
Recognizing the centrality of team-based care to diabetes management, our team has developed and implemented an enhanced primary care diabetes (EPCD) model across the internal medicine and family medicine practices of Mayo Clinic, first in Rochester, Minnesota and then across multiple rural and small urban sites in southeast Minnesota. This model is centered around the primary care team nurse, who partners with clinicians to oversee, enforce, and coordinate the diabetes management of patients paneled to those clinicians. Nurses proactively identify patients, engage other members of the healthcare team (eg, pharmacists, social workers, certified diabetes care and education specialists) as needed, and maintain a continuous relationship with each patient to help them achieve and maintain their goals. This model was not only effective at improving glycemic control and other indicators of diabetes care quality, but also improved nursing and clinician satisfaction.
It is important to recognize that comprehensive diabetes care comprises both medical and nonmedical interventions that address the totality of the patient’s care needs and the circumstances that hinder optimal health. Increasingly, robust data are emerging in support of nonmedical interventions that target SDoH, including structural racism as a root cause of racial and ethnic disparities in diabetes care and outcomes, with demonstrated evidence of improved health outcomes and narrowed health disparities.
It takes work, effort, and commitment to manage diabetes. But a team-based approach allows players on all sides to win.
Those of us who treat patients with type 2 diabetes (T2D) daily have long recognized a disturbing irony: diabetes is a disease whose management requires consistency in approach and constancy in delivery, but it is most prevalent among those whose lives often allow little to no time for either.
In our clinic, many patients with diabetes are struggling, in some way, to incorporate diabetes management into their daily lives. They are juggling multiple jobs and family responsibilities; they are working jobs with inconsistent access to food or refrigeration (such as farming, service industry work, and others); and many—even those with insurance—are struggling to afford their insulin and non insulin medications, insulin administration supplies, and glucose testing equipment.
Studies show how stress deleteriously affects this disease. The body does not deal well with these frequent and persistent stressors; higher cortisol levels result in higher blood glucose levels, increased systemic inflammation, and other drivers of both diabetes and its complications; all have been extensively documented.
What has been frustrating for our clinical community is knowing that since the early 2000s, new diabetes medications and technologies have been available that can make a difference in our patients’ lives, but for various reasons, they have not been well adopted, particularly among patients most likely to benefit from them. Consequently, we have not consistently seen meaningfully reduced glycated hemoglobin (A1c) levels or reduced rates of acute or chronic diabetes complications. Therapeutic inertia exists at the patient, systemic, and physician levels.
Many of the new glucose-lowering medications can also improve cardiovascular and kidney disease outcomes with low risk for hypoglycemia and weight gain. Diabetes technologies like insulin pumps and continuous glucose monitors (CGM) have been demonstrated in clinical trials to improve A1c and reduce hypoglycemia risk. But the reality is that clinicians are seeing an increasing number of patients with high A1c, with hypoglycemia, with severe hyperglycemia, and with long-term diabetes complications.
If these advancements are supposed to improve health outcomes, why are patient, community, and population health not improving? Why are some patients not receiving the care they need, while others get extra services that do not improve their health and may even harm them?
These advancements also create new questions for clinicians. At what point in the disease course should existing medications be ramped up, ramped down, or changed? Which patient characteristics or comorbidities allow or do not allow these changes? When should we use technologies or when does their burden outweigh their potential benefits? What resources and support systems do our patients need to live well with their disease and how can these be procured?
Herein lies the problem: Diabetes is a dynamic disease that needs to be handled in a dynamic way, and that has not universally—or even frequently—occurred. Management must be a team endeavor, meaning that both patient and clinician must be proactive in diabetes management. It has been our experience, demonstrated in our work and in other studies, that success relies on a robust and comprehensive primary care system whose team members—physicians, advanced practice providers, nurses, pharmacists, certified diabetes care and education specialists, social workers, nurses, pharmacists, and dietitians—are all resilient and motivated to tackle one of the most complex, multifaceted, and multidimensional chronic health conditions in our practice.
Proactivity also includes consistent monitoring, learning from successes and failures, and public reporting. For the patient, proactive involvement generally means self-care multiple times a day.
Let us now discuss the evidence that prompted our team’s proactive approach to caring for people living with diabetes.
Gauges and perspective
The prevalence of T2D in this country stands at 11.3% within the adult population. Between 2015 and 2020, death from diabetes increased by 27%.
For years, the research community has documented the wide range of socioeconomic factors that increase the risk for developing T2D and that, once developed, make it more difficult for patients to manage their disease and achieve optimal health outcomes that are possible with available medications and technologies.
In 2019, Kazemian et al published work that examined the indicators of diabetes management progress (eg, A1c levels, cholesterol levels) of 1742 individuals, from 2005 to 2016. Just 23% to 25% of these patients achieved all goals, even though, during the study period, numerous medications were approved to manage disease better. Arguably, these should have improved the all-goal findings in the study.
The first injectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) was approved in 2005; between 2013 and 2016, the FDA also approved 4 sodium-glucose cotransporter 2 (SGLT2) inhibitors. Both medication classes can safely and effectively lower A1c with no weight gain and low risk for hypoglycemia. Over the past 4 years, a robust body of evidence has emerged to show that GLP-1 RAs and SGLT2 inhibitors not only lower A1c, but also reduce the likelihood of death from cardiovascular and kidney diseases. SGLT2 inhibitors are better at saving lives from hypertensive heart failure while the GLP-1 RAs are more protective from atherosclerotic cardiovascular events like myocardial infarction and stroke, as compared with placebo. Yet, these medications have not been, and continue not to be, regularly prescribed. In 1 study, the authors found that the rate of use for SGLT2 inhibitors was 3.8% in 2015 and 11.9% in 2019.
But there are several other reasons that patients do not receive these medicines.
Insurance
We conducted a retrospective cohort study of 382,574 adults between 58 and 66 years of age, insured by either a Medicare Advantage plan or commercial insurance, and compared treatment initiation of the 3 most common brand-name, second-line diabetes medications (as opposed to generic sulfonylureas), between 2016 and 2019. The rate of initiation was universally lower for Medicare Advantage members vs commercially insured individuals.
While the rates of initiation of GLP-1 RAs, SGLT2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors increased between 2016 and 2019, rates were significantly higher among patients with commercial insurance. Specifically, GLP-1 RA initiation increased from 2.1% to 20.0% among commercial insurance beneficiaries and from 1.5% to 11.4% among Medicare Advantage beneficiaries. SGLT2 inhibitor initiation increased from 2.7% to 18.2% with commercial insurance and from 1.57% to 8.51% with Medicare Advantage. DPP-4 inhibitor initiation increased from 3.3% to 11.7% with commercial insurance and from 2.44% to 7.68% with Medicare Advantage. Within each calendar year, the odds of initiating one of these 3 medications with Medicare Advantage as compared with commercial insurance ranged from 0.28 to 0.70 for GLP-1 RAs; from 0.21 to 0.57 for SGLT2 inhibitors; and from 0.37 to 0.73 for DPP-4 inhibitors.
We also looked at the initiation of these medications in individuals with cardiorenal comorbidities. In many cases, a drug was prescribed indiscriminately. A patient who would benefit from a GLP-1 RA because of cardiovascular, cerebrovascular, or kidney disease was less likely to be prescribed a GLP-1 RA than a medication like a DPP-4 inhibitor, which usually has the same formulary tier/class but does not have any of the cardiovascular or kidney benefits. Likewise, in those with heart failure or kidney disease, an SGLT2 inhibitor would have been the appropriate choice, but these patients were too often started on a DPP-4 inhibitor, which is not advised for those with heart failure and does provide kidney benefits.
Last year, Tummalapalli et al, in their evaluation of 4135 US health plans, including commercial- or employer-based, Medicare, Medicaid, and other public health plans, identified multiple barriers to accessing SGLT2 inhibitor medications. While all plans included at least 1 SGLT2 inhibitor on their formularies, they restricted access in other ways. Prior authorizations were required by nearly half of Medicaid plans and nearly 40% of other public plans such as the Veterans Health Administration. Medicare and other public plans commonly imposed quantity limits on fills. Commercial plans frequently (up to 40%) required step therapy (use or failure of a generic diabetes medication) before approval. Copayments were also high in commercial plans, Medicare, and others.
The need for prior authorizations dominates attempts to prescribe. Centene Corporation, for example, which manages plans for private and public payers, will not approve use of an SGLT2 inhibitor until the patient fails for 3 consecutive months on a prior treatment, has established cardiovascular disease or diabetic nephropathy, or has multiple cardiovascular risk factors. These comorbidities must be documented and verified, and the prior authorizations must be completed, often resulting in substantial administrative burden to clinicians. No wonder many, especially in primary care, may be wary of prescribing drugs that come with a paperwork trail and hours spent on documentation and insurance appeals, rather than on patient care.
The same can be said for prescribing a GLP-1 RA. United Healthcare’s Oxford Benefit Management requires that clinicians show a “history of suboptimal response, contraindication, or intolerance to metformin” before prescribing any of the 8 GLP-1 RAs.
The average retail cost of 30 empagliflozin tablets, a once-daily medication, is $752. During the pandemic, 24% of the 5000 patients surveyed in an American Diabetes Association (ADA) poll used their stimulus check, relied on loans, or spent savings to pay for diabetes care. GLP-1 RA medications are even more expensive. Depending on the patient’s pharmacy benefits, they may have to pay a substantial coinsurance out of pocket even after the annual deductible is met, creating financial barriers to starting and continuing recommended, evidence-based medications. Even if patients do get the recommended medications, they may be forced to ration other aspects of their lives, including other medications, food, and other necessities.
There are other important barriers to optimal utilization of evidence-based therapies, stemming from the fundamental social determinants of health: low income, low education level, and living in a socioeconomically deprived neighborhood.
Social Determinants of Health
Diabetes prevalence is higher in patients experiencing socioeconomic and other structural barriers to health and health care. Fundamentally, 1 study showed that prevalence of diabetes was 1.4 times higher among people living on less than $15,000 a year, as opposed to those earning at least $50,000 a year.
The risk of diabetes complications is also higher in individuals experiencing food or housing insecurity, those who have low income or education level, and residents in rural and socioeconomically deprived neighborhoods. Importantly, the same patient populations are also less likely to receive timely evidence-based care, contributing to and worsening health disparities. Despite their prevalence and importance, social determinants of health (SDoH) are not routinely recognized or discussed during clinical encounters, such that improving diabetes care and health outcomes is predicated on developing a system to screen for, recognize, and address the wide range of barriers faced by our patients. If a patient cannot afford a new medication or get to the clinic on a regular basis, lacks access to healthy food, or does not have time for diabetes self-management education or to focus on their health, then their well-being will suffer.
Many of these SDoH disproportionately affect racial and ethnic minority populations as the direct result of longstanding and deeply embedded systems, policies, and laws that underlie disparities in diabetes incidence, prevalence, management, and outcomes. As such, structural racism is increasingly recognized as a root cause of health disparities in diabetes and other chronic health conditions.
Proactive strategies
Since reactive care has not and cannot provide patients with the help they need and deserve, many in the diabetes care community have turned to proactive, team-based care. The Chronic Care Model, established in the 1990s, stresses decision-making support, strong team organization and delivery system design, and the wherewithal to monitor progress continually. Research has shown that the best results for patients stem from a multidisciplinary, data-driven, and proactive approach to identifying and meeting the totality of patient care needs.
The ADA stresses the importance of comprehensive, team-based care for successful management of diabetes. This includes expanding the role of teams to implement evidence-based diabetes care, using electronic health record tools to support timely and guideline-recommended delivery of services, empowering and educating patients and caregivers, eliciting and addressing financial and psychosocial barriers to care, and identifying, developing, and engaging community resources to support better health and well-being.
Recognizing the centrality of team-based care to diabetes management, our team has developed and implemented an enhanced primary care diabetes (EPCD) model across the internal medicine and family medicine practices of Mayo Clinic, first in Rochester, Minnesota and then across multiple rural and small urban sites in southeast Minnesota. This model is centered around the primary care team nurse, who partners with clinicians to oversee, enforce, and coordinate the diabetes management of patients paneled to those clinicians. Nurses proactively identify patients, engage other members of the healthcare team (eg, pharmacists, social workers, certified diabetes care and education specialists) as needed, and maintain a continuous relationship with each patient to help them achieve and maintain their goals. This model was not only effective at improving glycemic control and other indicators of diabetes care quality, but also improved nursing and clinician satisfaction.
It is important to recognize that comprehensive diabetes care comprises both medical and nonmedical interventions that address the totality of the patient’s care needs and the circumstances that hinder optimal health. Increasingly, robust data are emerging in support of nonmedical interventions that target SDoH, including structural racism as a root cause of racial and ethnic disparities in diabetes care and outcomes, with demonstrated evidence of improved health outcomes and narrowed health disparities.
It takes work, effort, and commitment to manage diabetes. But a team-based approach allows players on all sides to win.
Those of us who treat patients with type 2 diabetes (T2D) daily have long recognized a disturbing irony: diabetes is a disease whose management requires consistency in approach and constancy in delivery, but it is most prevalent among those whose lives often allow little to no time for either.
In our clinic, many patients with diabetes are struggling, in some way, to incorporate diabetes management into their daily lives. They are juggling multiple jobs and family responsibilities; they are working jobs with inconsistent access to food or refrigeration (such as farming, service industry work, and others); and many—even those with insurance—are struggling to afford their insulin and non insulin medications, insulin administration supplies, and glucose testing equipment.
Studies show how stress deleteriously affects this disease. The body does not deal well with these frequent and persistent stressors; higher cortisol levels result in higher blood glucose levels, increased systemic inflammation, and other drivers of both diabetes and its complications; all have been extensively documented.
What has been frustrating for our clinical community is knowing that since the early 2000s, new diabetes medications and technologies have been available that can make a difference in our patients’ lives, but for various reasons, they have not been well adopted, particularly among patients most likely to benefit from them. Consequently, we have not consistently seen meaningfully reduced glycated hemoglobin (A1c) levels or reduced rates of acute or chronic diabetes complications. Therapeutic inertia exists at the patient, systemic, and physician levels.
Many of the new glucose-lowering medications can also improve cardiovascular and kidney disease outcomes with low risk for hypoglycemia and weight gain. Diabetes technologies like insulin pumps and continuous glucose monitors (CGM) have been demonstrated in clinical trials to improve A1c and reduce hypoglycemia risk. But the reality is that clinicians are seeing an increasing number of patients with high A1c, with hypoglycemia, with severe hyperglycemia, and with long-term diabetes complications.
If these advancements are supposed to improve health outcomes, why are patient, community, and population health not improving? Why are some patients not receiving the care they need, while others get extra services that do not improve their health and may even harm them?
These advancements also create new questions for clinicians. At what point in the disease course should existing medications be ramped up, ramped down, or changed? Which patient characteristics or comorbidities allow or do not allow these changes? When should we use technologies or when does their burden outweigh their potential benefits? What resources and support systems do our patients need to live well with their disease and how can these be procured?
Herein lies the problem: Diabetes is a dynamic disease that needs to be handled in a dynamic way, and that has not universally—or even frequently—occurred. Management must be a team endeavor, meaning that both patient and clinician must be proactive in diabetes management. It has been our experience, demonstrated in our work and in other studies, that success relies on a robust and comprehensive primary care system whose team members—physicians, advanced practice providers, nurses, pharmacists, certified diabetes care and education specialists, social workers, nurses, pharmacists, and dietitians—are all resilient and motivated to tackle one of the most complex, multifaceted, and multidimensional chronic health conditions in our practice.
Proactivity also includes consistent monitoring, learning from successes and failures, and public reporting. For the patient, proactive involvement generally means self-care multiple times a day.
Let us now discuss the evidence that prompted our team’s proactive approach to caring for people living with diabetes.
Gauges and perspective
The prevalence of T2D in this country stands at 11.3% within the adult population. Between 2015 and 2020, death from diabetes increased by 27%.
For years, the research community has documented the wide range of socioeconomic factors that increase the risk for developing T2D and that, once developed, make it more difficult for patients to manage their disease and achieve optimal health outcomes that are possible with available medications and technologies.
In 2019, Kazemian et al published work that examined the indicators of diabetes management progress (eg, A1c levels, cholesterol levels) of 1742 individuals, from 2005 to 2016. Just 23% to 25% of these patients achieved all goals, even though, during the study period, numerous medications were approved to manage disease better. Arguably, these should have improved the all-goal findings in the study.
The first injectable glucagon-like peptide 1 receptor agonist (GLP-1 RA) was approved in 2005; between 2013 and 2016, the FDA also approved 4 sodium-glucose cotransporter 2 (SGLT2) inhibitors. Both medication classes can safely and effectively lower A1c with no weight gain and low risk for hypoglycemia. Over the past 4 years, a robust body of evidence has emerged to show that GLP-1 RAs and SGLT2 inhibitors not only lower A1c, but also reduce the likelihood of death from cardiovascular and kidney diseases. SGLT2 inhibitors are better at saving lives from hypertensive heart failure while the GLP-1 RAs are more protective from atherosclerotic cardiovascular events like myocardial infarction and stroke, as compared with placebo. Yet, these medications have not been, and continue not to be, regularly prescribed. In 1 study, the authors found that the rate of use for SGLT2 inhibitors was 3.8% in 2015 and 11.9% in 2019.
But there are several other reasons that patients do not receive these medicines.
Insurance
We conducted a retrospective cohort study of 382,574 adults between 58 and 66 years of age, insured by either a Medicare Advantage plan or commercial insurance, and compared treatment initiation of the 3 most common brand-name, second-line diabetes medications (as opposed to generic sulfonylureas), between 2016 and 2019. The rate of initiation was universally lower for Medicare Advantage members vs commercially insured individuals.
While the rates of initiation of GLP-1 RAs, SGLT2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors increased between 2016 and 2019, rates were significantly higher among patients with commercial insurance. Specifically, GLP-1 RA initiation increased from 2.1% to 20.0% among commercial insurance beneficiaries and from 1.5% to 11.4% among Medicare Advantage beneficiaries. SGLT2 inhibitor initiation increased from 2.7% to 18.2% with commercial insurance and from 1.57% to 8.51% with Medicare Advantage. DPP-4 inhibitor initiation increased from 3.3% to 11.7% with commercial insurance and from 2.44% to 7.68% with Medicare Advantage. Within each calendar year, the odds of initiating one of these 3 medications with Medicare Advantage as compared with commercial insurance ranged from 0.28 to 0.70 for GLP-1 RAs; from 0.21 to 0.57 for SGLT2 inhibitors; and from 0.37 to 0.73 for DPP-4 inhibitors.
We also looked at the initiation of these medications in individuals with cardiorenal comorbidities. In many cases, a drug was prescribed indiscriminately. A patient who would benefit from a GLP-1 RA because of cardiovascular, cerebrovascular, or kidney disease was less likely to be prescribed a GLP-1 RA than a medication like a DPP-4 inhibitor, which usually has the same formulary tier/class but does not have any of the cardiovascular or kidney benefits. Likewise, in those with heart failure or kidney disease, an SGLT2 inhibitor would have been the appropriate choice, but these patients were too often started on a DPP-4 inhibitor, which is not advised for those with heart failure and does provide kidney benefits.
Last year, Tummalapalli et al, in their evaluation of 4135 US health plans, including commercial- or employer-based, Medicare, Medicaid, and other public health plans, identified multiple barriers to accessing SGLT2 inhibitor medications. While all plans included at least 1 SGLT2 inhibitor on their formularies, they restricted access in other ways. Prior authorizations were required by nearly half of Medicaid plans and nearly 40% of other public plans such as the Veterans Health Administration. Medicare and other public plans commonly imposed quantity limits on fills. Commercial plans frequently (up to 40%) required step therapy (use or failure of a generic diabetes medication) before approval. Copayments were also high in commercial plans, Medicare, and others.
The need for prior authorizations dominates attempts to prescribe. Centene Corporation, for example, which manages plans for private and public payers, will not approve use of an SGLT2 inhibitor until the patient fails for 3 consecutive months on a prior treatment, has established cardiovascular disease or diabetic nephropathy, or has multiple cardiovascular risk factors. These comorbidities must be documented and verified, and the prior authorizations must be completed, often resulting in substantial administrative burden to clinicians. No wonder many, especially in primary care, may be wary of prescribing drugs that come with a paperwork trail and hours spent on documentation and insurance appeals, rather than on patient care.
The same can be said for prescribing a GLP-1 RA. United Healthcare’s Oxford Benefit Management requires that clinicians show a “history of suboptimal response, contraindication, or intolerance to metformin” before prescribing any of the 8 GLP-1 RAs.
The average retail cost of 30 empagliflozin tablets, a once-daily medication, is $752. During the pandemic, 24% of the 5000 patients surveyed in an American Diabetes Association (ADA) poll used their stimulus check, relied on loans, or spent savings to pay for diabetes care. GLP-1 RA medications are even more expensive. Depending on the patient’s pharmacy benefits, they may have to pay a substantial coinsurance out of pocket even after the annual deductible is met, creating financial barriers to starting and continuing recommended, evidence-based medications. Even if patients do get the recommended medications, they may be forced to ration other aspects of their lives, including other medications, food, and other necessities.
There are other important barriers to optimal utilization of evidence-based therapies, stemming from the fundamental social determinants of health: low income, low education level, and living in a socioeconomically deprived neighborhood.
Social Determinants of Health
Diabetes prevalence is higher in patients experiencing socioeconomic and other structural barriers to health and health care. Fundamentally, 1 study showed that prevalence of diabetes was 1.4 times higher among people living on less than $15,000 a year, as opposed to those earning at least $50,000 a year.
The risk of diabetes complications is also higher in individuals experiencing food or housing insecurity, those who have low income or education level, and residents in rural and socioeconomically deprived neighborhoods. Importantly, the same patient populations are also less likely to receive timely evidence-based care, contributing to and worsening health disparities. Despite their prevalence and importance, social determinants of health (SDoH) are not routinely recognized or discussed during clinical encounters, such that improving diabetes care and health outcomes is predicated on developing a system to screen for, recognize, and address the wide range of barriers faced by our patients. If a patient cannot afford a new medication or get to the clinic on a regular basis, lacks access to healthy food, or does not have time for diabetes self-management education or to focus on their health, then their well-being will suffer.
Many of these SDoH disproportionately affect racial and ethnic minority populations as the direct result of longstanding and deeply embedded systems, policies, and laws that underlie disparities in diabetes incidence, prevalence, management, and outcomes. As such, structural racism is increasingly recognized as a root cause of health disparities in diabetes and other chronic health conditions.
Proactive strategies
Since reactive care has not and cannot provide patients with the help they need and deserve, many in the diabetes care community have turned to proactive, team-based care. The Chronic Care Model, established in the 1990s, stresses decision-making support, strong team organization and delivery system design, and the wherewithal to monitor progress continually. Research has shown that the best results for patients stem from a multidisciplinary, data-driven, and proactive approach to identifying and meeting the totality of patient care needs.
The ADA stresses the importance of comprehensive, team-based care for successful management of diabetes. This includes expanding the role of teams to implement evidence-based diabetes care, using electronic health record tools to support timely and guideline-recommended delivery of services, empowering and educating patients and caregivers, eliciting and addressing financial and psychosocial barriers to care, and identifying, developing, and engaging community resources to support better health and well-being.
Recognizing the centrality of team-based care to diabetes management, our team has developed and implemented an enhanced primary care diabetes (EPCD) model across the internal medicine and family medicine practices of Mayo Clinic, first in Rochester, Minnesota and then across multiple rural and small urban sites in southeast Minnesota. This model is centered around the primary care team nurse, who partners with clinicians to oversee, enforce, and coordinate the diabetes management of patients paneled to those clinicians. Nurses proactively identify patients, engage other members of the healthcare team (eg, pharmacists, social workers, certified diabetes care and education specialists) as needed, and maintain a continuous relationship with each patient to help them achieve and maintain their goals. This model was not only effective at improving glycemic control and other indicators of diabetes care quality, but also improved nursing and clinician satisfaction.
It is important to recognize that comprehensive diabetes care comprises both medical and nonmedical interventions that address the totality of the patient’s care needs and the circumstances that hinder optimal health. Increasingly, robust data are emerging in support of nonmedical interventions that target SDoH, including structural racism as a root cause of racial and ethnic disparities in diabetes care and outcomes, with demonstrated evidence of improved health outcomes and narrowed health disparities.
It takes work, effort, and commitment to manage diabetes. But a team-based approach allows players on all sides to win.
Commentary: Treating Chronic Migraine and Providing Temporary Relief, July 2022
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.
The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.
The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.
Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.
Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.
The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.
Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.
Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.
This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.
The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.
This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.
The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.
The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.
Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.
Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.
The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.
Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.
Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.
This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.
The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.
This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.
Many of our patients with refractory migraine do not respond to first-line acute or preventive treatments, and, almost by definition, first- and second-line treatments have failed in the majority of patients on calcitonin gene-related peptide (CGRP) antagonist medications. Three studies this month highlight the efficacy of CGRP monoclonal antibody (mAb) and small-molecule medications in this population specifically.
Most headache specialists are familiar with the "standard" or PREEMPT onabotulinumtoxinA (Botox) paradigm used preventively for migraine. This protocol uses 155 units of onabotulinumtoxinA over 31 sites in seven muscle groups. OnabotulinumtoxinA vials typically come in 100 or 200 units, and when preparing onabotulinumtoxinA for patients who are being injected most providers are forced to discard most or all of the remaining 45 units. Anecdotally, some providers do inject the entire 200-unit vial, and the additional injection sites are either given in another standard protocol or in a follow-the-pain manner.
The study by Zandieh and colleagues followed 175 patients with chronic migraine who first received three injections of 150 units of onabotulinumtoxinA, then three injections of 200 units of this agent. The additional 50 units were injected into the temporalis and occipitalis muscles — the standard sites were used, but additional units were injected into each of the sites. The majority of patients experienced primarily frontal pain; the injections were not given in specific areas where more pain was manifesting.
The average number of headache days per month decreased significantly when the onabotulinumtoxinA dose was increased; patients tolerated the medication over the 3-month period as well. In practice, many providers use the additional units of onabotulinumtoxinA. This study argues that there is a minimal risk, and probably a potential significant benefit, when using up to 200 units every 3 months. Providers should, however, be aware that in rare instances, some insurances will only cover a 155-unit injection, and the use of additional units may jeopardize reimbursement for those plans.
Many patients anecdotally will use cold or heat as a treatment for acute migraine pain; however, the topical use of temperature has not been well studied for this purpose. Cold stimulus has, importantly, been known to be a trigger of migraine as well as other headache disorders classified in the International Classification of Headache Disorders, third edition (ICHD-3), including external cold stimulus headache and "brain freeze" or internal cold stimulus headache. Hsu and colleagues produced a meta-analysis and systematic review on the use of cold for acute treatment of migraine.
Six studies were found to be eligible for this review. The cold stimulus could be placed anywhere on the head, and the studies could have considered its use for any migraine-associated symptom. This includes headache, eye pain, nausea, or vomiting. The interventions used cold somewhat differently, including as ice packing, cooling compression, soaking, and as a rinse. Both randomized and nonrandomized trials were included in the systematic review; however, only randomized controlled trials were used for the meta-analysis.
The primary outcome evaluated by the authors was pain intensity; secondary outcomes were duration of migraine pain as well as associated symptoms (eg, nausea, vomiting). The meta-analysis revealed that cold interventions reduce migraine pain by 3.21 points on an analog scale, and this was found to be effective within 30 minutes. At 1-2 hours after the intervention, the effect was not seen to be significant. At 24 hours, the effect of cold intervention was marginal. Cold was not seen to significantly reduce nausea or vomiting at 2 hours after intervention.
Although cold treatments are commonly used by patients, there appears to be benefit only early in the onset of a migraine attack. Headache specialists typically recommend early treatment with a migraine-specific acute medication; however, the medication may take minutes to hours before taking effect. Cold can be recommended to patients during that intervening period, and it may help until the time that their acute medications take effect.
Chronic refractory migraine remains one of the most debilitating neurologic disorders and is a challenge even for the best trained neurologist or headache specialist. There are few headache centers with inpatient headache units around the United States, and those that remain use treatments that most neurologists are not familiar with. Schwenk and colleagues retrospectively reviewed the data of a major academic headache center and revealed impressive outcomes in this very difficult-to-treat population.
This study reviewed the outcomes of 609 consecutive patients admitted to the Thomas Jefferson University inpatient headache unit from 2017 to 2021. These patients all received continuous lidocaine infusions that were titrated according to an internal protocol that balanced daily plasma lidocaine levels, tolerability, and pain relief. Hospital discharge occurred when patients were pain-free for 12-24 hours or had a minimal response after 5 days of treatment. All patients had at least eight severe headaches per month for at least 6 consecutive months and had tried one to seven preventive medications, with the result of either intolerance or ineffectiveness.
The primary outcome was change from baseline to discharge pain level. Patients were admitted with an average score of 7.0 of 10 on admission and were discharged at a score of 1.0 of 10. Secondary outcomes were average pain at post-discharge appointment vs baseline (5.5 vs 7.0), number of monthly headache days at post-discharge appointment (22.5 vs 26.8), and current and average pain levels at the post-discharge appointment, which were both significantly lower as well. The most common adverse effect was nausea; others noted were cardiovascular changes, hallucinations or nightmares, sedation, anxiety, and chest pain.
This is an important retrospective on the effectiveness of an inpatient lidocaine protocol for refractory chronic migraine. When considering this population, especially if multiple lines of preventive and acute medications are not effective, referral to an academic inpatient headache center should definitely be considered. This patient population does not respond effectively to most treatment modalities, and this is cause to give them hope.