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10% of US physicians work for or under UnitedHealth. Is that a problem?
as more payers and private equity firms pursue medical practice acquisitions.
The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.
Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care.
Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied.
Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization.
Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh.
A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce.
The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized.
According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws.
The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care.
“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.”
Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee.
Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers.
UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders.
At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.
A version of this article appeared on Medscape.com.
as more payers and private equity firms pursue medical practice acquisitions.
The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.
Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care.
Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied.
Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization.
Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh.
A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce.
The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized.
According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws.
The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care.
“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.”
Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee.
Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers.
UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders.
At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.
A version of this article appeared on Medscape.com.
as more payers and private equity firms pursue medical practice acquisitions.
The company added 20,000 physicians in the last year alone, including a previously physician-owned multispecialty group practice of 400 doctors in New York. They join the growing web of doctors — about 90,000 of the 950,000 active US physicians — working for the UnitedHealth Group subsidiary, Optum Health, providing primary, specialty, urgent, and surgical care. Amar Desai, MD, chief executive officer of Optum Health, shared the updated workforce numbers during the health care conglomerate’s annual investor conference.
Health care mergers and consolidations have become more common as physician groups struggle to stay afloat amid dwindling payer reimbursements. Although private equity and health systems often acquire practices, payers like UHC are increasingly doing so as part of their model to advance value-based care.
Yashaswini Singh, PhD, health care economist and assistant professor of health services, policy, and practice at Brown University, says such moves mirror the broader trend in corporate consolidation of physician practices. She said in an interview that the integrated models could possibly enhance care coordination and improve outcomes, but the impact of payer-led consolidation has not been extensively studied.
Meanwhile, evidence considering private equity ownership is just emerging. In a 2022 study published in JAMA Health Forum, with Dr. Singh as lead author, findings showed that private equity involvement increased healthcare spending through higher prices and utilization.
Consolidation can also raise anti-trust concerns. “If payers incentivize referral patterns of their employed physicians to favor other physicians employed by the payer, it can reduce competition by restricting consumer choice,” said Dr. Singh.
A potential merger between Cigna and Humana that could happen by the end of the year will likely face intense scrutiny as it would create a company that rivals the size of UnitedHealth Group or CVS Health. If it goes through, the duo could streamline its insurance offerings and leverage each other’s care delivery platforms, clinics, and provider workforce.
The Biden Administration has sought to strengthen anti-trust statutes to prevent industry monopolies and consumer harm, and the US Department of Justice and Federal Trade Commission have proposed new merger guidelines that have yet to be finalized.
According to Dr. Singh, some of Optum’s medical practice purchases may bypass anti-trust statutes since most prospective mergers and acquisitions are reviewed only if they exceed a specific value ($101 million for 2023). Limited transparency in ownership structures further complicates matters. Plus, Dr. Singh said instances where physicians are hired instead of acquired through mergers would not be subject to current anti-trust laws.
The ‘corporatization’ of health care is not good for patients or physicians, said Robert McNamara, MD, chief medical officer of the American Academy of Emergency Medicine Physician Group and cofounder of Take Medicine Back, a physician group advocating to remove corporate interests from health care.
“If you ask a physician what causes them the most moral conflict, they’ll tell you it’s the insurance companies denying something they want to do for their patients,” he said. “To have the doctors now working for the insurance industry conflicts with a physician’s duty to put the patient first.”
Dr. McNamara, chair of emergency medicine at Temple University’s Katz School of Medicine, said in an interview that more than half the states in the United States have laws or court rulings that support protecting physician autonomy from corporate interests. Still, he hopes a federal prohibition on private equity’s involvement in healthcare can soon gain traction. In November, Take Medicine Back raised a resolution at the American Medical Association’s interim House of Delegates meeting, which he said was subsequently referred to a committee.
Emergency medicine was among the first specialties to succumb to private equity firms, but Dr. McNamara said that all types of health care providers and entities — from cardiology and urology to addiction treatment centers and nursing homes — are being swallowed up by larger organizations, including payers.
UHC was named in a class action suit recently for allegedly shirking doctors’ orders and relying on a flawed algorithm to determine the length of skilled nursing facility stays for Medicare Advantage policyholders.
At the investor meeting, Dr. Desai reiterated Optum’s desire to continue expanding care delivery options, especially in its pharmacy and behavioral health business lines, and focus on adopting value-based care. He credited the rapid growth to developing strong relationships with providers and standardizing technology and clinical systems.
A version of this article appeared on Medscape.com.
U.S. Task Force Takes on Rising BMIs Among Children
The U.S. Preventive Services Task Force — a team of independent, volunteer experts in disease prevention who guide doctors’ decisions and influence insurance coverage — issued a draft recommendation statement outlining the interventions that should be taken when a child or teen has a high body mass index.
Nearly 20% of children between 2 and 19 years old have what are considered high BMIs, according to Centers for Disease Control and Prevention data. While adults who have a BMI of 30 or higher are considered to have obesity, childhood obesity is determined if a child is at or above the 95th percentile of others their age and gender.
Given the prevalence of the issue, the task force recommends behavioral interventions that include at least 26 hours of supervised physical activity sessions for up to a year. This differs from the task force’s previous recommendations on the topic, which emphasized the importance of screening for high BMIs rather than describing the right ways to intervene.
Some of the most effective interventions are targeted at both parents and their children, whether that be together, separately, or a combination of the two. Additionally, the task force recommends that children attend group sessions about healthy eating habits, how to read food labels, and exercise techniques. Ideally, these would be led and guided by people of various professional backgrounds like pediatricians, physical therapists, dietitians, psychologists, and social workers. Other medical organizations, namely the American Academy of Pediatrics, have recommended medication for some children with obesity; the task force, however, takes a more conservative approach. They noted that although the body of evidence shows weight loss medications and surgery are effective for many, there isn’t enough research to lean on regarding the use of these interventions in children, especially in the long term.
“There are proven ways that clinicians can help the many children and teens who have a high BMI to manage their weight and stay healthy,” said Katrina Donahue, MD, MPH, a member of the task force and professor of family medicine at the University of North Carolina at Chapel Hill. “Intensive behavioral interventions are effective in helping children achieve a healthy weight while improving quality of life.”
The guidelines are still in the draft stage and are available for public comment until Jan. 16, 2024.
A version of this article appeared on WebMD.com.
The U.S. Preventive Services Task Force — a team of independent, volunteer experts in disease prevention who guide doctors’ decisions and influence insurance coverage — issued a draft recommendation statement outlining the interventions that should be taken when a child or teen has a high body mass index.
Nearly 20% of children between 2 and 19 years old have what are considered high BMIs, according to Centers for Disease Control and Prevention data. While adults who have a BMI of 30 or higher are considered to have obesity, childhood obesity is determined if a child is at or above the 95th percentile of others their age and gender.
Given the prevalence of the issue, the task force recommends behavioral interventions that include at least 26 hours of supervised physical activity sessions for up to a year. This differs from the task force’s previous recommendations on the topic, which emphasized the importance of screening for high BMIs rather than describing the right ways to intervene.
Some of the most effective interventions are targeted at both parents and their children, whether that be together, separately, or a combination of the two. Additionally, the task force recommends that children attend group sessions about healthy eating habits, how to read food labels, and exercise techniques. Ideally, these would be led and guided by people of various professional backgrounds like pediatricians, physical therapists, dietitians, psychologists, and social workers. Other medical organizations, namely the American Academy of Pediatrics, have recommended medication for some children with obesity; the task force, however, takes a more conservative approach. They noted that although the body of evidence shows weight loss medications and surgery are effective for many, there isn’t enough research to lean on regarding the use of these interventions in children, especially in the long term.
“There are proven ways that clinicians can help the many children and teens who have a high BMI to manage their weight and stay healthy,” said Katrina Donahue, MD, MPH, a member of the task force and professor of family medicine at the University of North Carolina at Chapel Hill. “Intensive behavioral interventions are effective in helping children achieve a healthy weight while improving quality of life.”
The guidelines are still in the draft stage and are available for public comment until Jan. 16, 2024.
A version of this article appeared on WebMD.com.
The U.S. Preventive Services Task Force — a team of independent, volunteer experts in disease prevention who guide doctors’ decisions and influence insurance coverage — issued a draft recommendation statement outlining the interventions that should be taken when a child or teen has a high body mass index.
Nearly 20% of children between 2 and 19 years old have what are considered high BMIs, according to Centers for Disease Control and Prevention data. While adults who have a BMI of 30 or higher are considered to have obesity, childhood obesity is determined if a child is at or above the 95th percentile of others their age and gender.
Given the prevalence of the issue, the task force recommends behavioral interventions that include at least 26 hours of supervised physical activity sessions for up to a year. This differs from the task force’s previous recommendations on the topic, which emphasized the importance of screening for high BMIs rather than describing the right ways to intervene.
Some of the most effective interventions are targeted at both parents and their children, whether that be together, separately, or a combination of the two. Additionally, the task force recommends that children attend group sessions about healthy eating habits, how to read food labels, and exercise techniques. Ideally, these would be led and guided by people of various professional backgrounds like pediatricians, physical therapists, dietitians, psychologists, and social workers. Other medical organizations, namely the American Academy of Pediatrics, have recommended medication for some children with obesity; the task force, however, takes a more conservative approach. They noted that although the body of evidence shows weight loss medications and surgery are effective for many, there isn’t enough research to lean on regarding the use of these interventions in children, especially in the long term.
“There are proven ways that clinicians can help the many children and teens who have a high BMI to manage their weight and stay healthy,” said Katrina Donahue, MD, MPH, a member of the task force and professor of family medicine at the University of North Carolina at Chapel Hill. “Intensive behavioral interventions are effective in helping children achieve a healthy weight while improving quality of life.”
The guidelines are still in the draft stage and are available for public comment until Jan. 16, 2024.
A version of this article appeared on WebMD.com.
Report: CKD Severity Linked to Thinning of Retina, Choroid Layers
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
Changes in tissue thickness in the back of the eye can correlate with worsening or improvement of renal problems and could help predict who will have worsening of kidney function, a new analysis report finds.
The research, published in the journal Nature Communications, is the first to show an association between chronic kidney disease (CKD) and the thickness of the retinal and choroidal layers in the back of the eye as measured by optical coherence tomography (OCT), a noninvasive imaging technology commonly used to evaluate eye diseases such as age-related macular degeneration (AMD), diabetic eye disease, and retinal detachments.
“These are common scans that people get at the opticians and now in many hospitals,” said Neeraj Dhaun, MD, PhD, a professor of nephrology at the University of Edinburgh, Scotland. (Opticians in the United Kingdom are the equivalent of optometrists in North America.)
CKD Severity Equals Thinner Retinas
“We scanned the back of eye of healthy people as well as patients with various types and degrees of kidney disease, and we found that two layers in the back of eye, the retina and the choroid, were thinner in patients with kidney disease compared to people who are healthy, and that the extent of this thinning predicts whether kidney function would decline going forward over a period of 2 or 3 years,” Dr. Dhaun, the corresponding author of the new paper, said.
The publication is a report of four different studies. The first study measured OCT metrics in 112 patients with CKD, 92 patients with a functional kidney transplant, and 86 control volunteers. The researchers found the retina was 5% thinner in patients with CKD than in healthy controls. They also found that patients with CKD had reduced macular volume: 8.44 ± .44 mm3 vs 8.73 ± .36 mm3 (P < .001). The choroid was also found to be thinner at each of three macular locations measured in patients with CKD vs control volunteers. At baseline, CKD and transplant patients had significantly lower estimated glomerular filtration rate (eGFR) at 55 ± 27 and 55 ± 24 mL/min/1.73 m2 compared with control volunteers at 97 ± 14 mL/min/1.73 m2.
The second study reported on OCT measurements and kidney histologic injury in 50 patients who had a kidney biopsy within 30 days of their OCT. It found that choroidal thinning at all three macular locations was independently associated with more extensive kidney scarring.
The third study focused on 25 patients with kidney failure who had a kidney transplant. Their eGFR improved from 8 ± 3 to 58 ± 21 mL/min/1.73 m2 in the first week after the transplant. The choroid in these patients thickened about 5% at 1 week and by about 10% at 1 month posttransplant. OCT of 22 kidney donors showed thickening of the choroid a week after nephrectomy before a tendency to thinning over the next year.
The fourth study found that for patients with stable CKD, every 1 mm3 decrease in macular volume correlated to an increased odds of a decline in eGFR by more than 10% at 1 year (2.48; 95% CI, 1.26-5.08; P = .01) and by more than 20% at 2 years (3.75; 95% CI, 1.26-5.08; P = .004).
Exploring the Kidney-Eye Connection
The potential explanation for the correlation between retinal and choroidal thickness and kidney function is unclear, Dr. Dhaun said.
“We don’t know the exact mechanisms, and these are difficult to define from studies in patients, which is why we are doing more work in animal models of kidney disease to see if we can establish the pathways that lead to the changes in the eye,” he said.
“However,” Dr. Dhaun added, “what we do know is that kidney disease affects the whole body. For example, kidney disease can lead to high blood pressure and heart disease, as well as diseases in the brain, and it is these effects of kidney disease on the body as whole that we are probably picking up in the back of the eye.”
OCT has the potential to make the monitoring of patients with CKD and kidney transplant more convenient than it is now, Dr. Dhaun said. “These scanners are available in the community, and what would be ideal at some point in the future is to be able to do a patient’s kidney health check in the community potentially incorporating OCT scanning alongside blood-pressure monitoring and other healthcare measures,” he said.
“The findings provide an exciting example of how noninvasive retinal imaging using OCT can provide quantitative biomarkers of systemic disease,” Amir Kashani, MD, PhD, the Boone Pickens Professor of Ophthalmology and Biomedical Engineering at the Wilmer Eye Institute of Johns Hopkins University in Baltimore, told this news organization. “It is striking that their findings demonstrate some potential of reversible changes in choroidal perfusion after kidney transplantation.”
The finding that choroidal thickness changes in CKD are at least partly reversible with kidney transplantation is a revelation, Dr. Kashani said, and may point to a greater role for ophthalmologists in managing systemic disease.
“Ophthalmologists can and should use their unique experience and understanding of the eye to help monitor and manage systemic conditions in collaboration with our medicine colleagues,” he said. “There are many systemic diseases that can impact the eye and ophthalmologist are uniquely positioned to help interpret those findings.”
Dr. Kashani noted that a particular strength of the report was the comparison of choroidal measurements in patients who had kidney transplantation and those that had a nephrectomy. “The consistent direction of changes in these two groups suggests the study findings are real and meaningful,” he said.
The study was independently supported. Dr. Dhaun and co-authors report no relevant financial relationships. Dr. Kashani disclosed a financial relationship with Carl Zeiss Meditec.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
Supercharge your medical practice with ChatGPT: Here’s why you should upgrade
Artificial intelligence (AI) has already demonstrated its potential in various areas of healthcare, from early disease detection and drug discovery to genomics and personalized care. OpenAI’s ChatGPT, a large language model, is one AI tool that has been transforming practices across the globe, including mine.
Let me walk you through it.
ChatGPT is essentially an AI-fueled assistant, capable of interpreting and generating human-like text in response to user inputs. Imagine a well-informed and competent trainee working with you, ready to tackle tasks from handling patient inquiries to summarizing intricate medical literature.
Currently, ChatGPT works on the “freemium” pricing model; there is a free version built upon GPT-3.5 as well as a subscription “ChatGPT Plus” version based on GPT-4 which offers additional features such as the use of third-party plug-ins.
Now, you may ask, “Isn’t the free version enough?” The free version is indeed impressive, but upgrading to the paid version for $20 per month unlocks the full potential of this tool, particularly if we add plug-ins.
Here are some of the best ways to incorporate ChatGPT Plus into your practice.
Time saver and efficiency multiplier. The paid version of ChatGPT is an extraordinary time-saving tool. It can help you sort through vast amounts of medical literature in a fraction of the time it would normally take. Imagine having to sift through hundreds of articles to find the latest research relevant to a patient’s case. With the paid version of ChatGPT, you can simply ask it to provide summaries of the most recent and relevant studies, all in seconds.
Did you forget about that PowerPoint you need to make but know the potential papers you would use? No problem. ChatGPT can create slides in a few minutes. It becomes your on-demand research assistant.
Of course, you need to provide the source you find most relevant to you. Using plug-ins such as ScholarAI and Link Reader are great.
Improved patient communication. Explaining complex medical terminology and procedures to patients can sometimes be a challenge. ChatGPT can generate simplified and personalized explanations for your patients, fostering their understanding and involvement in their care process.
Epic is currently collaborating with Nuance Communications, Microsoft’s speech recognition subsidiary, to use generative AI tools for medical note-taking in the electronic health record. However, you do not need to wait for it; it just takes a prompt in ChatGPT and then copying/pasting the results into the chart.
Smoother administrative management. The premium version of ChatGPT can automate administrative tasks such as creating letters of medical necessity, clearance to other physicians for services, or even communications to staff on specific topics. This frees you to focus more on your core work: providing patient care.
Precision medicine aid. ChatGPT can be a powerful ally in the field of precision medicine. Its capabilities for analyzing large datasets and unearthing valuable insights can help deliver more personalized and potentially effective treatment plans. For example, one can prompt ChatGPT to query the reported frequency of certain genomic variants and their implications; with the upgraded version and plug-ins, the results will have fewer hallucinations — inaccurate results — and key data references.
Unlimited accessibility. Uninterrupted access is a compelling reason to upgrade. While the free version may have usage limitations, the premium version provides unrestricted, round-the-clock access. Be it a late-night research quest or an early-morning patient query, your AI assistant will always be available.
Strengthened privacy and security. The premium version of ChatGPT includes heightened privacy and security measures. Just make sure to follow HIPAA and not include identifiers when making queries.
Embracing AI tools like ChatGPT in your practice can help you stay at the cutting edge of medical care, saving you time, enhancing patient communication, and supporting you in providing personalized care.
While the free version can serve as a good starting point (there are apps for both iOS and Android), upgrading to the paid version opens up a world of possibilities that can truly supercharge your practice.
I would love to hear your comments on this column or on future topics. Contact me at Arturo.AI.MedTech@gmail.com.
Arturo Loaiza-Bonilla, MD, MSEd, is the cofounder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr. Loaiza-Bonilla is Assistant Professor of Medicine, Drexel University School of Medicine, Philadelphia, Pennsylvania, and serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has financial relationships with Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, Guardant, Amgen, Eisai, Natera, Merck, and Bristol Myers Squibb.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) has already demonstrated its potential in various areas of healthcare, from early disease detection and drug discovery to genomics and personalized care. OpenAI’s ChatGPT, a large language model, is one AI tool that has been transforming practices across the globe, including mine.
Let me walk you through it.
ChatGPT is essentially an AI-fueled assistant, capable of interpreting and generating human-like text in response to user inputs. Imagine a well-informed and competent trainee working with you, ready to tackle tasks from handling patient inquiries to summarizing intricate medical literature.
Currently, ChatGPT works on the “freemium” pricing model; there is a free version built upon GPT-3.5 as well as a subscription “ChatGPT Plus” version based on GPT-4 which offers additional features such as the use of third-party plug-ins.
Now, you may ask, “Isn’t the free version enough?” The free version is indeed impressive, but upgrading to the paid version for $20 per month unlocks the full potential of this tool, particularly if we add plug-ins.
Here are some of the best ways to incorporate ChatGPT Plus into your practice.
Time saver and efficiency multiplier. The paid version of ChatGPT is an extraordinary time-saving tool. It can help you sort through vast amounts of medical literature in a fraction of the time it would normally take. Imagine having to sift through hundreds of articles to find the latest research relevant to a patient’s case. With the paid version of ChatGPT, you can simply ask it to provide summaries of the most recent and relevant studies, all in seconds.
Did you forget about that PowerPoint you need to make but know the potential papers you would use? No problem. ChatGPT can create slides in a few minutes. It becomes your on-demand research assistant.
Of course, you need to provide the source you find most relevant to you. Using plug-ins such as ScholarAI and Link Reader are great.
Improved patient communication. Explaining complex medical terminology and procedures to patients can sometimes be a challenge. ChatGPT can generate simplified and personalized explanations for your patients, fostering their understanding and involvement in their care process.
Epic is currently collaborating with Nuance Communications, Microsoft’s speech recognition subsidiary, to use generative AI tools for medical note-taking in the electronic health record. However, you do not need to wait for it; it just takes a prompt in ChatGPT and then copying/pasting the results into the chart.
Smoother administrative management. The premium version of ChatGPT can automate administrative tasks such as creating letters of medical necessity, clearance to other physicians for services, or even communications to staff on specific topics. This frees you to focus more on your core work: providing patient care.
Precision medicine aid. ChatGPT can be a powerful ally in the field of precision medicine. Its capabilities for analyzing large datasets and unearthing valuable insights can help deliver more personalized and potentially effective treatment plans. For example, one can prompt ChatGPT to query the reported frequency of certain genomic variants and their implications; with the upgraded version and plug-ins, the results will have fewer hallucinations — inaccurate results — and key data references.
Unlimited accessibility. Uninterrupted access is a compelling reason to upgrade. While the free version may have usage limitations, the premium version provides unrestricted, round-the-clock access. Be it a late-night research quest or an early-morning patient query, your AI assistant will always be available.
Strengthened privacy and security. The premium version of ChatGPT includes heightened privacy and security measures. Just make sure to follow HIPAA and not include identifiers when making queries.
Embracing AI tools like ChatGPT in your practice can help you stay at the cutting edge of medical care, saving you time, enhancing patient communication, and supporting you in providing personalized care.
While the free version can serve as a good starting point (there are apps for both iOS and Android), upgrading to the paid version opens up a world of possibilities that can truly supercharge your practice.
I would love to hear your comments on this column or on future topics. Contact me at Arturo.AI.MedTech@gmail.com.
Arturo Loaiza-Bonilla, MD, MSEd, is the cofounder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr. Loaiza-Bonilla is Assistant Professor of Medicine, Drexel University School of Medicine, Philadelphia, Pennsylvania, and serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has financial relationships with Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, Guardant, Amgen, Eisai, Natera, Merck, and Bristol Myers Squibb.
A version of this article appeared on Medscape.com.
Artificial intelligence (AI) has already demonstrated its potential in various areas of healthcare, from early disease detection and drug discovery to genomics and personalized care. OpenAI’s ChatGPT, a large language model, is one AI tool that has been transforming practices across the globe, including mine.
Let me walk you through it.
ChatGPT is essentially an AI-fueled assistant, capable of interpreting and generating human-like text in response to user inputs. Imagine a well-informed and competent trainee working with you, ready to tackle tasks from handling patient inquiries to summarizing intricate medical literature.
Currently, ChatGPT works on the “freemium” pricing model; there is a free version built upon GPT-3.5 as well as a subscription “ChatGPT Plus” version based on GPT-4 which offers additional features such as the use of third-party plug-ins.
Now, you may ask, “Isn’t the free version enough?” The free version is indeed impressive, but upgrading to the paid version for $20 per month unlocks the full potential of this tool, particularly if we add plug-ins.
Here are some of the best ways to incorporate ChatGPT Plus into your practice.
Time saver and efficiency multiplier. The paid version of ChatGPT is an extraordinary time-saving tool. It can help you sort through vast amounts of medical literature in a fraction of the time it would normally take. Imagine having to sift through hundreds of articles to find the latest research relevant to a patient’s case. With the paid version of ChatGPT, you can simply ask it to provide summaries of the most recent and relevant studies, all in seconds.
Did you forget about that PowerPoint you need to make but know the potential papers you would use? No problem. ChatGPT can create slides in a few minutes. It becomes your on-demand research assistant.
Of course, you need to provide the source you find most relevant to you. Using plug-ins such as ScholarAI and Link Reader are great.
Improved patient communication. Explaining complex medical terminology and procedures to patients can sometimes be a challenge. ChatGPT can generate simplified and personalized explanations for your patients, fostering their understanding and involvement in their care process.
Epic is currently collaborating with Nuance Communications, Microsoft’s speech recognition subsidiary, to use generative AI tools for medical note-taking in the electronic health record. However, you do not need to wait for it; it just takes a prompt in ChatGPT and then copying/pasting the results into the chart.
Smoother administrative management. The premium version of ChatGPT can automate administrative tasks such as creating letters of medical necessity, clearance to other physicians for services, or even communications to staff on specific topics. This frees you to focus more on your core work: providing patient care.
Precision medicine aid. ChatGPT can be a powerful ally in the field of precision medicine. Its capabilities for analyzing large datasets and unearthing valuable insights can help deliver more personalized and potentially effective treatment plans. For example, one can prompt ChatGPT to query the reported frequency of certain genomic variants and their implications; with the upgraded version and plug-ins, the results will have fewer hallucinations — inaccurate results — and key data references.
Unlimited accessibility. Uninterrupted access is a compelling reason to upgrade. While the free version may have usage limitations, the premium version provides unrestricted, round-the-clock access. Be it a late-night research quest or an early-morning patient query, your AI assistant will always be available.
Strengthened privacy and security. The premium version of ChatGPT includes heightened privacy and security measures. Just make sure to follow HIPAA and not include identifiers when making queries.
Embracing AI tools like ChatGPT in your practice can help you stay at the cutting edge of medical care, saving you time, enhancing patient communication, and supporting you in providing personalized care.
While the free version can serve as a good starting point (there are apps for both iOS and Android), upgrading to the paid version opens up a world of possibilities that can truly supercharge your practice.
I would love to hear your comments on this column or on future topics. Contact me at Arturo.AI.MedTech@gmail.com.
Arturo Loaiza-Bonilla, MD, MSEd, is the cofounder and chief medical officer at Massive Bio, a company connecting patients to clinical trials using artificial intelligence. His research and professional interests focus on precision medicine, clinical trial design, digital health, entrepreneurship, and patient advocacy. Dr. Loaiza-Bonilla is Assistant Professor of Medicine, Drexel University School of Medicine, Philadelphia, Pennsylvania, and serves as medical director of oncology research at Capital Health in New Jersey, where he maintains a connection to patient care by attending to patients 2 days a week. He has financial relationships with Verify, PSI CRO, Bayer, AstraZeneca, Cardinal Health, BrightInsight, The Lynx Group, Fresenius, Pfizer, Ipsen, Guardant, Amgen, Eisai, Natera, Merck, and Bristol Myers Squibb.
A version of this article appeared on Medscape.com.
What if a single GLP-1 shot could last for months?
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
As revolutionary as glucagon-like peptide 1 (GLP-1) drugs are, they still last for only so long in the body. Patients with diabetes typically must be injected once or twice a day (liraglutide) or once a week (semaglutide). This could hinder proper diabetes management, as adherence tends to go down the more frequent the dose.
But what if a single GLP-1 injection could last for 4 months?
“melts away like a sugar cube dissolving in water, molecule by molecule,” said Eric Appel, PhD, the project’s principal investigator and an associate professor of materials science and engineering at Stanford (Calif.) University.
So far, the team has tested the new drug delivery system in rats, and they say human clinical trials could start within 2 years.
Mathematical modeling indicated that one shot of liraglutide could maintain exposure in humans for 120 days, or about 4 months, according to their study in Cell Reports Medicine.
“Patient adherence is of critical importance to diabetes care,” said Alex Abramson, PhD, assistant professor in the chemical and biomolecular engineering department at Georgia Tech, who was not involved in the study. “It’s very exciting to have a potential new system that can last 4 months on a single injection.”
Long-Acting Injectables Have Come a Long Way
The first long-acting injectable — Lupron Depot, a monthly treatment for advanced prostate cancer — was approved in 1989. Since then, long-acting injectable depots have revolutionized the treatment and management of conditions ranging from osteoarthritis knee pain to schizophrenia to opioid use disorder. In 2021, the US Food and Drug Administration approved Apretude — an injectable treatment for HIV pre-exposure prevention that needs to be given every 2 months, compared with daily for the pill equivalent. Other new and innovative developments are underway: Researchers at the University of Connecticut are working on a transdermal microneedle patch — with many tiny vaccine-loaded needles — that could provide multiple doses of a vaccine over time, no boosters needed.
At Stanford, Appel’s lab has spent years developing gels for drug delivery. His team uses a class of hydrogel called polymer-nanoparticle (PNP), which features weakly bound polymers and nanoparticles that can dissipate slowly over time.
The goal is to address a longstanding challenge with long-acting formulations: Achieving steady release. Because the hydrogel is “self-healing” — able to repair damages and restore its shape — it’s less likely to burst and release its drug cargo too early.
“Our PNP hydrogels possess a number of really unique characteristics,” Dr. Appel said. They have “excellent” biocompatibility, based on animal studies, and could work with a wide range of drugs. In proof-of-concept mouse studies, Dr. Appel and his team have shown that these hydrogels could also be used to make vaccines last longer, ferry cancer immunotherapies directly to tumors, and deliver antibodies for the prevention of infectious diseases like SARS-CoV-2.
Though the recent study on GLP-1s focused on treating type 2 diabetes, the same formulation could also be used to treat obesity, said Dr. Appel.
The researchers tested the tech using two GLP-1 receptor agonists — semaglutide and liraglutide. In rats, one shot maintained therapeutic serum concentrations of semaglutide or liraglutide over 42 days. With semaglutide, a significant portion was released quickly, followed by controlled release. Liraglutide, on the other hand, was released gradually as the hydrogel dissolved. This suggests the liraglutide hydrogel may be better tolerated, as a sudden peak in drug serum concentration is associated with adverse effects.
The researchers used pharmacokinetic modeling to predict how liraglutide would behave in humans with a larger injection volume, finding that a single dose could maintain therapeutic levels for about 4 months.
“Moving forward, it will be important to determine whether a burst release from the formulation causes any side effects,” Dr. Abramson noted. “Furthermore, it will be important to minimize the injection volumes in humans.”
But first, more studies in larger animals are needed. Next, Dr. Appel and his team plan to test the technology in pigs, whose skin and endocrine systems are most like humans’. If those trials go well, Dr. Appel said, human clinical trials could start within 2 years.
A version of this article appeared on Medscape.com.
FROM CELL REPORTS MEDICINE
Electronic Health Records — Recent Survey Results
I have been writing about electronic health records since the mid-1990s. While the basic concept has always been sound, I have always been (and continue to be) a critic of its implementation, which I have compared to the work of the Underpants Gnomes from the television show South Park.
You may recall that Phase One of the Gnomes’ grand scheme was to collect underpants, and Phase Three was to reap enormous profits. Unfortunately, they never quite figured out Phase Two.
EHR’s problems have run a similar course, ever since George W. Bush introduced the EHR Incentive Program (later renamed the Promoting Interoperability Program) in 2000. “By computerizing health records,” the president said, “we can avoid dangerous medical mistakes, reduce costs, and improve care.” That was the ultimate goal — Phase Three, if you will — but nearly a quarter-century later, we are still struggling with Phase Two.
According to the results of a recent survey by this news organization, progress has been made, but issues with usability, reliability, and patient privacy remain.
surveys, respectively. But 56% of them continue to worry about harmful effects from incorrect or misdirected information as a result of inputs from multiple sources, and the rapid turnover of staff that is doing the inputting. Many doctors worry about the potential for incorrect medications and “rule out” diagnoses getting embedded in some patients’ records and undermining future care.
The lack of information sharing among different EHR systems has been the technology’s greatest unmet promise, according to the survey. A lack of interoperability was cited as the most common reason for switching EHR systems. Other reasons included difficulties in clinical documentation and extracting data for quality reporting, as well as the inability to merge inpatient and outpatient records.
A clear majority (72%) felt EHR systems are getting easier to use. The recent decrease in government mandates has freed vendors to work on improving ease of documentation and information retrieval. The incorporation of virtual assistants and other artificial intelligence–based features (as I discussed in two recent columns) have also contributed to improved overall usability. Some newer applications even allow users to build workarounds to compensate for inherent deficiencies in the system.
Physicians tended to be most praiseworthy of functions related to electronic prescribing and retrieval of individual patient data. They felt that much more improvement was needed in helpful prompt features, internal messaging, and communications from patients.
The survey found that 38% of physicians “always” or “often” copy and paste information in patient charts, with another 37% doing so “occasionally.” Noting some of the problems inherent in copy and paste, such as note bloat, internal inconsistencies, error propagation, and documentation in the wrong patient chart, the survey authors suggest that EHR developers could help by shifting away from timelines that appear as one long note. They could also add functionality to allow new information to be displayed as updates on a digital chart.
Improvement is also needed in the way the EHR affects patient interactions, according to the survey results. Physicians are still often forced to click to a different screen to find lab results, another for current medications, and still another for past notes, all while trying to communicate with the patient. Such issues are likely to decrease in the next few years as doctors gain the ability to give voice commands to AI-based system add-ons to obtain this information.
Security concerns seem to be decreasing. In this year’s survey, nearly half of all physicians voiced no EHR privacy problems or concerns, even though a recent review of medical literature concluded that security risks remain meaningful. Those who did have privacy concerns were mostly worried about hackers and other unauthorized access to patient information.
The survey found that around 40% of EHR systems are not using patient portals to post lab results, diagnoses and procedure notes, or prescriptions. However, other physicians complained that their systems were too prompt in posting results, so that patients often received them before the doctor did. This is certainly another area where improvement at both extremes is necessary.
Other areas in which physicians saw a need for improvement were in system reliability, user training, and ongoing customer service. And among the dwindling ranks of physicians with no EHR experience, the most common reasons given for refusing to invest in an EHR system were affordability and interference with the doctor-patient relationship.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
I have been writing about electronic health records since the mid-1990s. While the basic concept has always been sound, I have always been (and continue to be) a critic of its implementation, which I have compared to the work of the Underpants Gnomes from the television show South Park.
You may recall that Phase One of the Gnomes’ grand scheme was to collect underpants, and Phase Three was to reap enormous profits. Unfortunately, they never quite figured out Phase Two.
EHR’s problems have run a similar course, ever since George W. Bush introduced the EHR Incentive Program (later renamed the Promoting Interoperability Program) in 2000. “By computerizing health records,” the president said, “we can avoid dangerous medical mistakes, reduce costs, and improve care.” That was the ultimate goal — Phase Three, if you will — but nearly a quarter-century later, we are still struggling with Phase Two.
According to the results of a recent survey by this news organization, progress has been made, but issues with usability, reliability, and patient privacy remain.
surveys, respectively. But 56% of them continue to worry about harmful effects from incorrect or misdirected information as a result of inputs from multiple sources, and the rapid turnover of staff that is doing the inputting. Many doctors worry about the potential for incorrect medications and “rule out” diagnoses getting embedded in some patients’ records and undermining future care.
The lack of information sharing among different EHR systems has been the technology’s greatest unmet promise, according to the survey. A lack of interoperability was cited as the most common reason for switching EHR systems. Other reasons included difficulties in clinical documentation and extracting data for quality reporting, as well as the inability to merge inpatient and outpatient records.
A clear majority (72%) felt EHR systems are getting easier to use. The recent decrease in government mandates has freed vendors to work on improving ease of documentation and information retrieval. The incorporation of virtual assistants and other artificial intelligence–based features (as I discussed in two recent columns) have also contributed to improved overall usability. Some newer applications even allow users to build workarounds to compensate for inherent deficiencies in the system.
Physicians tended to be most praiseworthy of functions related to electronic prescribing and retrieval of individual patient data. They felt that much more improvement was needed in helpful prompt features, internal messaging, and communications from patients.
The survey found that 38% of physicians “always” or “often” copy and paste information in patient charts, with another 37% doing so “occasionally.” Noting some of the problems inherent in copy and paste, such as note bloat, internal inconsistencies, error propagation, and documentation in the wrong patient chart, the survey authors suggest that EHR developers could help by shifting away from timelines that appear as one long note. They could also add functionality to allow new information to be displayed as updates on a digital chart.
Improvement is also needed in the way the EHR affects patient interactions, according to the survey results. Physicians are still often forced to click to a different screen to find lab results, another for current medications, and still another for past notes, all while trying to communicate with the patient. Such issues are likely to decrease in the next few years as doctors gain the ability to give voice commands to AI-based system add-ons to obtain this information.
Security concerns seem to be decreasing. In this year’s survey, nearly half of all physicians voiced no EHR privacy problems or concerns, even though a recent review of medical literature concluded that security risks remain meaningful. Those who did have privacy concerns were mostly worried about hackers and other unauthorized access to patient information.
The survey found that around 40% of EHR systems are not using patient portals to post lab results, diagnoses and procedure notes, or prescriptions. However, other physicians complained that their systems were too prompt in posting results, so that patients often received them before the doctor did. This is certainly another area where improvement at both extremes is necessary.
Other areas in which physicians saw a need for improvement were in system reliability, user training, and ongoing customer service. And among the dwindling ranks of physicians with no EHR experience, the most common reasons given for refusing to invest in an EHR system were affordability and interference with the doctor-patient relationship.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
I have been writing about electronic health records since the mid-1990s. While the basic concept has always been sound, I have always been (and continue to be) a critic of its implementation, which I have compared to the work of the Underpants Gnomes from the television show South Park.
You may recall that Phase One of the Gnomes’ grand scheme was to collect underpants, and Phase Three was to reap enormous profits. Unfortunately, they never quite figured out Phase Two.
EHR’s problems have run a similar course, ever since George W. Bush introduced the EHR Incentive Program (later renamed the Promoting Interoperability Program) in 2000. “By computerizing health records,” the president said, “we can avoid dangerous medical mistakes, reduce costs, and improve care.” That was the ultimate goal — Phase Three, if you will — but nearly a quarter-century later, we are still struggling with Phase Two.
According to the results of a recent survey by this news organization, progress has been made, but issues with usability, reliability, and patient privacy remain.
surveys, respectively. But 56% of them continue to worry about harmful effects from incorrect or misdirected information as a result of inputs from multiple sources, and the rapid turnover of staff that is doing the inputting. Many doctors worry about the potential for incorrect medications and “rule out” diagnoses getting embedded in some patients’ records and undermining future care.
The lack of information sharing among different EHR systems has been the technology’s greatest unmet promise, according to the survey. A lack of interoperability was cited as the most common reason for switching EHR systems. Other reasons included difficulties in clinical documentation and extracting data for quality reporting, as well as the inability to merge inpatient and outpatient records.
A clear majority (72%) felt EHR systems are getting easier to use. The recent decrease in government mandates has freed vendors to work on improving ease of documentation and information retrieval. The incorporation of virtual assistants and other artificial intelligence–based features (as I discussed in two recent columns) have also contributed to improved overall usability. Some newer applications even allow users to build workarounds to compensate for inherent deficiencies in the system.
Physicians tended to be most praiseworthy of functions related to electronic prescribing and retrieval of individual patient data. They felt that much more improvement was needed in helpful prompt features, internal messaging, and communications from patients.
The survey found that 38% of physicians “always” or “often” copy and paste information in patient charts, with another 37% doing so “occasionally.” Noting some of the problems inherent in copy and paste, such as note bloat, internal inconsistencies, error propagation, and documentation in the wrong patient chart, the survey authors suggest that EHR developers could help by shifting away from timelines that appear as one long note. They could also add functionality to allow new information to be displayed as updates on a digital chart.
Improvement is also needed in the way the EHR affects patient interactions, according to the survey results. Physicians are still often forced to click to a different screen to find lab results, another for current medications, and still another for past notes, all while trying to communicate with the patient. Such issues are likely to decrease in the next few years as doctors gain the ability to give voice commands to AI-based system add-ons to obtain this information.
Security concerns seem to be decreasing. In this year’s survey, nearly half of all physicians voiced no EHR privacy problems or concerns, even though a recent review of medical literature concluded that security risks remain meaningful. Those who did have privacy concerns were mostly worried about hackers and other unauthorized access to patient information.
The survey found that around 40% of EHR systems are not using patient portals to post lab results, diagnoses and procedure notes, or prescriptions. However, other physicians complained that their systems were too prompt in posting results, so that patients often received them before the doctor did. This is certainly another area where improvement at both extremes is necessary.
Other areas in which physicians saw a need for improvement were in system reliability, user training, and ongoing customer service. And among the dwindling ranks of physicians with no EHR experience, the most common reasons given for refusing to invest in an EHR system were affordability and interference with the doctor-patient relationship.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at dermnews@mdedge.com.
How to prescribe Zepbound
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes, 
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes,
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
December marks the advent of the approval of tirzepatide (Zepbound) for on-label treatment of obesity. In November 2023, the US Food and Drug Administration (FDA) approved it for the treatment of obesity in adults.
In May 2022, the FDA approved Mounjaro, which is tirzepatide, for type 2 diabetes. Since then, many physicians, including myself, have prescribed it off-label for obesity. As an endocrinologist treating both obesity and diabetes,
The Expertise
Because GLP-1 receptor agonists have been around since 2005, we’ve had over a decade of clinical experience with these medications. Table 2 provides more nuanced information on tirzepatide (as Zepbound, for obesity) based on our experiences with dulaglutide, liraglutide, semaglutide, and tirzepatide (as Mounjaro).
The Reality
In today’s increasingly complex healthcare system, the reality of providing high-quality obesity care is challenging. When discussing tirzepatide with patients, I use a 4 Cs schematic — comorbidities, cautions, costs, choices — to cover the most frequently asked questions.
Comorbidities
In trials, tirzepatide reduced A1c by about 2%. In one diabetes trial, tirzepatide reduced liver fat content significantly more than the comparator (insulin), and trials of tirzepatide in nonalcoholic steatohepatitis are ongoing. A prespecified meta-analysis of tirzepatide and cardiovascular disease estimated a 20% reduction in the risk for cardiovascular death, myocardial infarction, stroke, and hospitalized unstable angina. Tirzepatide as well as other GLP-1 agonists may be beneficial in alcohol use disorder. Prescribing tirzepatide to patients who have or are at risk of developing such comorbidities is an ideal way to target multiple metabolic diseases with one agent.
Cautions
The first principle of medicine is “do no harm.” Tirzepatide may be a poor option for individuals with a history of pancreatitis, gastroparesis, or severe gastroesophageal reflux disease. Because tirzepatide may interfere with the efficacy of estrogen-containing contraceptives during its uptitration phase, women should speak with their doctors about appropriate birth control options (eg, progestin-only, barrier methods). In clinical trials of tirzepatide, male participants were also advised to use reliable contraception. If patients are family-planning, tirzepatide should be discontinued 2 months (for women) and 4 months (for men) before conception, because its effects on fertility or pregnancy are currently unknown.
Costs
At a retail price of $1279 per month, Zepbound is only slightly more affordable than its main competitor, Wegovy (semaglutide 2.4 mg). Complex pharmacy negotiations may reduce this cost, but even with rebates, coupons, and commercial insurance, these costs still place tirzepatide out of reach for many patients. For patients who cannot access tirzepatide, clinicians should discuss more cost-feasible, evidence-based alternatives: for example, phentermine, phentermine-topiramate, naltrexone-bupropion, metformin, bupropion, or topiramate.
Choices
Patient preference drives much of today’s clinical decision-making. Some patients may be switching from semaglutide to tirzepatide, whether by choice or on the basis of physician recommendation. Although no head-to-head obesity trial exists, data from SURPASS-2 and SUSTAIN-FORTE can inform therapeutic equivalence:
- Semaglutide 1.0 mg to tirzepatide 2.5 mg will be a step-down; 5 mg will be a step-up
- Semaglutide 2.0 or 2.4 mg to tirzepatide 5 mg is probably equivalent
The decision to switch therapeutics may depend on weight loss goals, side effect tolerability, or insurance coverage. As with all medications, the use of tirzepatide should progress with shared decision-making, thorough discussions of risks vs benefits, and individualized regimens tailored to each patient’s needs.
The newly approved Zepbound is a valuable addition to our toolbox of obesity treatments. Patients and providers alike are excited for its potential as a highly effective antiobesity medication that can cause a degree of weight loss necessary to reverse comorbidities. The medical management of obesity with agents like tirzepatide holds great promise in addressing today’s obesity epidemic.
Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed ties to Gelesis and Novo Nordisk.
A version of this article appeared on Medscape.com.
What is the link between cellphones and male fertility?
Infertility affects approximately one in six couples worldwide. More than half the time, it is the man’s low sperm quality that is to blame. Over the last three decades, sperm quality seems to have declined for no clearly identifiable reason. Theories are running rampant without anyone having the proof to back them up.
Potential Causes
The environment, lifestyle, excess weight or obesity, smoking, alcohol consumption, and psychological stress have all been alternately offered up as potential causes, following low-quality epidemiological studies. Cellphones are not exempt from this list, due to their emission of high-frequency (800-2200 MHz) electromagnetic waves that can be absorbed by the body.
Clinical trials conducted in rats or mice suggest that these waves can affect sperm quality and lead to histological changes to the testicles, bearing in mind that the conditions met in these trials are very far from our day-to-day exposure to electromagnetic waves, mostly via our cellphones.
The same observation can be made about experiments conducted on human sperm in vitro, but changes to the latter caused by electromagnetic waves leave doubts. Observational studies are rare, carried out in small cohorts, and marred by largely conflicting results. Publication bias plays a major role, just as much as the abundance of potential confounding factors does.
Swiss Observational Study
An observational study carried out in Switzerland had the benefit of involving a large cohort of 2886 young men who were representative of the general population. The participants completed an online questionnaire describing their relationship with their cellphone in detail and in qualitative and quantitative terms.
The study was launched in 2005, before cellphone use became so widespread, and this timeline was considered when looking for a link between cellphone exposure and sperm quality. In addition, multiple adjustments were made in the multivariate analyses to account for as many potential confounding factors as possible.
The participants, aged between 18 and 22 years, were recruited during a 3-day period to assess their suitability for military service. Each year, this cohort makes up 97% of the male population in Switzerland in this age range, with the remaining 3% being excluded from the selection process due to disability or chronic illness.
Regardless of the review board’s decision, subjects wishing to take part in the study were given a detailed description of what it involved, a consent form, and two questionnaires. The first focused on the individual directly, asking questions about his health and lifestyle. The second, intended for his parents, dealt with the period before conception.
This recruitment, which took place between September 2005 and November 2018, involved the researchers contacting 106,924 men. Ultimately, only 5.3% of subjects contacted returned the completed documentation. In the end, the study involved 2886 participants (3.1%) who provided all the necessary information, especially the laboratory testing (including a sperm analysis) needed to meet the study objectives. The number of hours spent on a smartphone and how it was used were routinely considered, as was sperm quality (volume, concentration, and total sperm count, as well as sperm mobility and morphology).
Significant Associations
A data analysis using an adjusted linear model revealed a significant association between frequent phone use (> 20 times per day) and lower sperm concentration (in mL) (adjusted β: -0.152, 95% CI -0.316 to 0.011). The same was found for their total concentration in ejaculate (adjusted β: -0.271, 95% CI -0.515 to -0.027).
An adjusted logistic regression analysis estimated that the risk for subnormal male fertility levels, as determined by the World Health Organization (WHO), was increased by at most 30%, when referring to the concentration of sperm per mL (21% in terms of total concentration). This inverse link was shown to be more pronounced during the first phase of the study (2005-2007), compared with the other two phases (2008-2011 and 2012-2018). Yet no links involving sperm mobility or morphology were found, and carrying a cellphone in a trouser pocket had no impact on the results.
This study certainly involves a large cohort of nearly 3000 young men. It is, nonetheless, retrospective, and its methodology, despite being better than that of previous studies, is still open to criticism. Its results can only fuel hypotheses, nothing more. Only prospective cohort studies will allow conclusions to be drawn and, in the meantime,
This article was translated from JIM, which is part of the Medscape professional network. A version of this article appeared on Medscape.com.
Infertility affects approximately one in six couples worldwide. More than half the time, it is the man’s low sperm quality that is to blame. Over the last three decades, sperm quality seems to have declined for no clearly identifiable reason. Theories are running rampant without anyone having the proof to back them up.
Potential Causes
The environment, lifestyle, excess weight or obesity, smoking, alcohol consumption, and psychological stress have all been alternately offered up as potential causes, following low-quality epidemiological studies. Cellphones are not exempt from this list, due to their emission of high-frequency (800-2200 MHz) electromagnetic waves that can be absorbed by the body.
Clinical trials conducted in rats or mice suggest that these waves can affect sperm quality and lead to histological changes to the testicles, bearing in mind that the conditions met in these trials are very far from our day-to-day exposure to electromagnetic waves, mostly via our cellphones.
The same observation can be made about experiments conducted on human sperm in vitro, but changes to the latter caused by electromagnetic waves leave doubts. Observational studies are rare, carried out in small cohorts, and marred by largely conflicting results. Publication bias plays a major role, just as much as the abundance of potential confounding factors does.
Swiss Observational Study
An observational study carried out in Switzerland had the benefit of involving a large cohort of 2886 young men who were representative of the general population. The participants completed an online questionnaire describing their relationship with their cellphone in detail and in qualitative and quantitative terms.
The study was launched in 2005, before cellphone use became so widespread, and this timeline was considered when looking for a link between cellphone exposure and sperm quality. In addition, multiple adjustments were made in the multivariate analyses to account for as many potential confounding factors as possible.
The participants, aged between 18 and 22 years, were recruited during a 3-day period to assess their suitability for military service. Each year, this cohort makes up 97% of the male population in Switzerland in this age range, with the remaining 3% being excluded from the selection process due to disability or chronic illness.
Regardless of the review board’s decision, subjects wishing to take part in the study were given a detailed description of what it involved, a consent form, and two questionnaires. The first focused on the individual directly, asking questions about his health and lifestyle. The second, intended for his parents, dealt with the period before conception.
This recruitment, which took place between September 2005 and November 2018, involved the researchers contacting 106,924 men. Ultimately, only 5.3% of subjects contacted returned the completed documentation. In the end, the study involved 2886 participants (3.1%) who provided all the necessary information, especially the laboratory testing (including a sperm analysis) needed to meet the study objectives. The number of hours spent on a smartphone and how it was used were routinely considered, as was sperm quality (volume, concentration, and total sperm count, as well as sperm mobility and morphology).
Significant Associations
A data analysis using an adjusted linear model revealed a significant association between frequent phone use (> 20 times per day) and lower sperm concentration (in mL) (adjusted β: -0.152, 95% CI -0.316 to 0.011). The same was found for their total concentration in ejaculate (adjusted β: -0.271, 95% CI -0.515 to -0.027).
An adjusted logistic regression analysis estimated that the risk for subnormal male fertility levels, as determined by the World Health Organization (WHO), was increased by at most 30%, when referring to the concentration of sperm per mL (21% in terms of total concentration). This inverse link was shown to be more pronounced during the first phase of the study (2005-2007), compared with the other two phases (2008-2011 and 2012-2018). Yet no links involving sperm mobility or morphology were found, and carrying a cellphone in a trouser pocket had no impact on the results.
This study certainly involves a large cohort of nearly 3000 young men. It is, nonetheless, retrospective, and its methodology, despite being better than that of previous studies, is still open to criticism. Its results can only fuel hypotheses, nothing more. Only prospective cohort studies will allow conclusions to be drawn and, in the meantime,
This article was translated from JIM, which is part of the Medscape professional network. A version of this article appeared on Medscape.com.
Infertility affects approximately one in six couples worldwide. More than half the time, it is the man’s low sperm quality that is to blame. Over the last three decades, sperm quality seems to have declined for no clearly identifiable reason. Theories are running rampant without anyone having the proof to back them up.
Potential Causes
The environment, lifestyle, excess weight or obesity, smoking, alcohol consumption, and psychological stress have all been alternately offered up as potential causes, following low-quality epidemiological studies. Cellphones are not exempt from this list, due to their emission of high-frequency (800-2200 MHz) electromagnetic waves that can be absorbed by the body.
Clinical trials conducted in rats or mice suggest that these waves can affect sperm quality and lead to histological changes to the testicles, bearing in mind that the conditions met in these trials are very far from our day-to-day exposure to electromagnetic waves, mostly via our cellphones.
The same observation can be made about experiments conducted on human sperm in vitro, but changes to the latter caused by electromagnetic waves leave doubts. Observational studies are rare, carried out in small cohorts, and marred by largely conflicting results. Publication bias plays a major role, just as much as the abundance of potential confounding factors does.
Swiss Observational Study
An observational study carried out in Switzerland had the benefit of involving a large cohort of 2886 young men who were representative of the general population. The participants completed an online questionnaire describing their relationship with their cellphone in detail and in qualitative and quantitative terms.
The study was launched in 2005, before cellphone use became so widespread, and this timeline was considered when looking for a link between cellphone exposure and sperm quality. In addition, multiple adjustments were made in the multivariate analyses to account for as many potential confounding factors as possible.
The participants, aged between 18 and 22 years, were recruited during a 3-day period to assess their suitability for military service. Each year, this cohort makes up 97% of the male population in Switzerland in this age range, with the remaining 3% being excluded from the selection process due to disability or chronic illness.
Regardless of the review board’s decision, subjects wishing to take part in the study were given a detailed description of what it involved, a consent form, and two questionnaires. The first focused on the individual directly, asking questions about his health and lifestyle. The second, intended for his parents, dealt with the period before conception.
This recruitment, which took place between September 2005 and November 2018, involved the researchers contacting 106,924 men. Ultimately, only 5.3% of subjects contacted returned the completed documentation. In the end, the study involved 2886 participants (3.1%) who provided all the necessary information, especially the laboratory testing (including a sperm analysis) needed to meet the study objectives. The number of hours spent on a smartphone and how it was used were routinely considered, as was sperm quality (volume, concentration, and total sperm count, as well as sperm mobility and morphology).
Significant Associations
A data analysis using an adjusted linear model revealed a significant association between frequent phone use (> 20 times per day) and lower sperm concentration (in mL) (adjusted β: -0.152, 95% CI -0.316 to 0.011). The same was found for their total concentration in ejaculate (adjusted β: -0.271, 95% CI -0.515 to -0.027).
An adjusted logistic regression analysis estimated that the risk for subnormal male fertility levels, as determined by the World Health Organization (WHO), was increased by at most 30%, when referring to the concentration of sperm per mL (21% in terms of total concentration). This inverse link was shown to be more pronounced during the first phase of the study (2005-2007), compared with the other two phases (2008-2011 and 2012-2018). Yet no links involving sperm mobility or morphology were found, and carrying a cellphone in a trouser pocket had no impact on the results.
This study certainly involves a large cohort of nearly 3000 young men. It is, nonetheless, retrospective, and its methodology, despite being better than that of previous studies, is still open to criticism. Its results can only fuel hypotheses, nothing more. Only prospective cohort studies will allow conclusions to be drawn and, in the meantime,
This article was translated from JIM, which is part of the Medscape professional network. A version of this article appeared on Medscape.com.
Children who are overweight at risk for chronic kidney disease
TOPLINE
, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.
METHODOLOGY
- The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
- The mean age at study entry was 17.2 and 54.5% were male.
- Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher.
- The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
- Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.
TAKEAWAY
- With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
- Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
- In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
- For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
- For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.
IN PRACTICE
“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report.
“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.
“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”
SOURCE
The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.
LIMITATIONS
The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.
DISCLOSURES
Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE
, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.
METHODOLOGY
- The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
- The mean age at study entry was 17.2 and 54.5% were male.
- Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher.
- The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
- Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.
TAKEAWAY
- With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
- Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
- In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
- For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
- For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.
IN PRACTICE
“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report.
“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.
“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”
SOURCE
The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.
LIMITATIONS
The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.
DISCLOSURES
Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
TOPLINE
, with the association, though weaker, still significant among those who do not develop type 2 diabetes or hypertension, in a large cohort study.
METHODOLOGY
- The study included data on 593,660 adolescents aged 16-20, born after January 1, 1975, who had medical assessments as part of mandatory military service in Israel.
- The mean age at study entry was 17.2 and 54.5% were male.
- Early CKD was defined as stage 1 to 2 CKD with moderately or severely increased albuminuria, with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or higher.
- The study excluded those with kidney pathology, albuminuria, hypertension, dysglycemia, or missing blood pressure or BMI data.
- Participants were followed up until early CKD onset, death, the last day insured, or August 23, 2020.
TAKEAWAY
- With a mean follow-up of 13.4 years, 1963 adolescents (0.3%) overall developed early chronic kidney disease. Among males, an increased risk of developing CKD was observed with a high-normal BMI in adolescence (hazard ratio [HR], 1.8); with overweight BMI (HR, 4.0); with mild obesity (HR, 6.7); and severe obesity (HR, 9.4).
- Among females, the increased risk was also observed with high-normal BMI (HR 1.4); overweight (HR, 2.3); mild obesity (HR, 2.7); and severe obesity (HR, 4.3).
- In excluding those who developed diabetes or hypertension, the overall rate of early CKD in the cohort was 0.2%.
- For males without diabetes or hypertension, the adjusted HR for early CKD with high-normal weight was 1.2; for overweight, HR 1.6; for mild obesity, HR 2.2; and for severe obesity, HR 2.7.
- For females without diabetes or hypertension, the corresponding increased risk for early CKD was HR 1.2 for high-normal BMI; HR 1.8 for overweight; 1.5 for mild obesity and 2.3 for severe obesity.
IN PRACTICE
“These findings suggest that adolescent obesity is a major risk factor for early CKD in young adulthood; this underscores the importance of mitigating adolescent obesity rates and managing risk factors for kidney disease in adolescents with high BMI,” the authors report.
“The association was evident even in persons with high-normal BMI in adolescence, was more pronounced in men, and appeared before the age of 30 years,” they say.
“Given the increasing obesity rates among adolescents, our findings are a harbinger of the potentially preventable increasing burden of CKD and subsequent cardiovascular disease.”
SOURCE
The study was conducted by first author Avishai M. Tsur, MD, of the Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel and Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel, and colleagues. The study was published online in JAMA Pediatrics.
LIMITATIONS
The study lacked longitudinal data on clinical and lifestyle factors, including stress, diet and physical activity. While adolescents were screened using urine dipstick, a lack of serum creatinine measurements could have missed some adolescents with reduced eGFR at the study entry. The generalizability of the results is limited by the lack of people from West Africa and East Asia in the study population.
DISCLOSURES
Coauthor Josef Coresh, MD, reported receiving grants from the National Institutes of Health outside the submitted work. No other disclosures were reported.
A version of this article appeared on Medscape.com.
New KDIGO guideline encourages use of HCV-positive kidneys for HCV-negative recipients
The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).
Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.
The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.
“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”
Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”
The updates are outlined below.
Expanded Access to HCV-Positive Kidneys
While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.
In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.
Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.
“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”
Dr. Rastogi agreed that this recommendation is the most impactful update.
“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”
For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.
In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.
“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”
This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
Sofosbuvir Given the Green Light
Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m2, including those receiving dialysis.
This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.
“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
Loosened Biopsy Requirements
Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.
“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.
If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
Individualizing Immunosuppressive Therapy
Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.
Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
More Work Is Needed
Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.
“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”
The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.
The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).
Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.
The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.
“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”
Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”
The updates are outlined below.
Expanded Access to HCV-Positive Kidneys
While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.
In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.
Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.
“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”
Dr. Rastogi agreed that this recommendation is the most impactful update.
“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”
For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.
In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.
“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”
This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
Sofosbuvir Given the Green Light
Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m2, including those receiving dialysis.
This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.
“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
Loosened Biopsy Requirements
Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.
“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.
If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
Individualizing Immunosuppressive Therapy
Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.
Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
More Work Is Needed
Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.
“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”
The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.
The Kidney Disease: Improving Global Outcomes (KDIGO) Work Group has updated its guideline concerning the prevention, diagnosis, evaluation, and treatment of hepatitis C virus (HCV) infection in patients with chronic kidney disease (CKD).
Of note, KDIGO now supports transplant of HCV-positive kidneys to HCV-negative recipients.
The guidance document, authored by Ahmed Arslan Yousuf Awan, MD, of Baylor College of Medicine, Houston, and colleagues, was written in light of new evidence that has emerged since the 2018 guideline was published.
“The focused update was triggered by new data on antiviral treatment in patients with advanced stages of CKD (G4, G5, or G5D), transplant of HCV-infected kidneys into uninfected recipients, and evolution of the viewpoint on the role of kidney biopsy in managing kidney disease caused by HCV,” the guideline panelists wrote in Annals of Internal Medicine. “This update is intended to assist clinicians in the care of patients with HCV infection and CKD, including patients receiving dialysis (CKD G5D) and patients with a kidney transplant (CKD G1T-G5T).”
Anjay Rastogi, MD, PhD, professor and clinical chief of nephrology at the David Geffen School of Medicine at UCLA, said the update is both “timely and relevant,” and “will really have an impact on the organ shortage that we have for kidney transplant”
The updates are outlined below.
Expanded Access to HCV-Positive Kidneys
While the 2018 guideline recommended that HCV-positive kidneys be directed to HCV-positive recipients, the new guideline suggests that these kidneys are appropriate for all patients regardless of HCV status.
In support, the panelists cited a follow-up of THINKER-1 trial, which showed that eGFR and quality of life were not negatively affected when HCV-negative patients received an HCV-positive kidney, compared with an HCV-negative kidney. Data from 525 unmatched recipients in 16 other studies support this conclusion, the panelists noted.
Jose Debes, MD, PhD, associate professor at the University of Minnesota, Minneapolis, suggested that this is the most important update to the KDIGO guidelines.
“That [change] would be the main impact of these recommendations,” Dr. Debes said in an interview. “Several centers were already doing this, since some data [were] out there, but I think the fact that they’re making this into a guideline is quite important.”
Dr. Rastogi agreed that this recommendation is the most impactful update.
“That’s a big move,” Dr. Rastogi said in an interview. He predicted that the change will “definitely increase the donor pool, which is very, very important.”
For this new recommendation to have the greatest positive effect, however, Dr. Rastogi suggested that health care providers and treatment centers need to prepare an effective implementation strategy. He emphasized the importance of early communication with patients concerning the safety of HCV-positive kidneys, which depends on early initiation of direct-acting antiviral (DAA) therapy.
In the guideline, Dr. Awan and colleagues reported three documented cases of fibrosing cholestatic hepatitis occurred in patients who did not begin DAA therapy until 30 days after transplant.
“[Patients] should start [DAA treatment] right away,” Dr. Rastogi said, “and sometimes even before the transplant.”
This will require institutional support, he noted, as centers need to ensure that patients are covered for DAA therapy and medication is readily available.
Sofosbuvir Given the Green Light
Compared with the 2018 guideline, which recommended against sofosbuvir in patients with CKD G4 and G5, including those on dialysis, because of concerns about metabolization via the kidneys, the new guideline suggests that sofosbuvir-based DAA regimens are appropriate in patients with glomerular filtration rate (GFR) less than 30 mL/min per 1.73 m2, including those receiving dialysis.
This recommendation was based on a systematic review of 106 studies including both sofosbuvir-based and non-sofosbuvir-based DAA regimens that showed high safety and efficacy for all DAA regimen types across a broad variety of patient types.
“DAAs are highly effective and well tolerated treatments for hepatitis C in patients across all stages of CKD, including those undergoing dialysis and kidney transplant recipients, with no need for dose adjustment,” Dr. Awan and colleagues wrote.
Loosened Biopsy Requirements
Unlike the 2018 guideline, which advised kidney biopsy in HCV-positive patients with clinical evidence of glomerular disease prior to initiating DAA treatment, the new guideline suggests that HCV-infected patients with a typical presentation of immune-complex proliferative glomerulonephritis do not require confirmatory kidney biopsy.
“Because almost all patients with chronic hepatitis C (with or without glomerulonephritis) should be treated with DAAs, a kidney biopsy is unlikely to change management in most patients with hepatitis C and clinical glomerulonephritis,” the panelists wrote.
If kidney disease does not stabilize or improve with achievement of sustained virologic response, or if there is evidence of rapidly progressive glomerulonephritis, then a kidney biopsy should be considered before beginning immunosuppressive therapy, according to the guideline, which includes a flow chart to guide clinicians through this decision-making process.
Individualizing Immunosuppressive Therapy
Consistent with the old guideline, the new guideline recommends DAA treatment with concurrent immunosuppressive therapy for patients with cryoglobulinemic flare or rapidly progressive kidney failure. But in contrast, the new guideline calls for an individualized approach to immunosuppression in patients with nephrotic syndrome.
Dr. Awan and colleagues suggested that “nephrotic-range proteinuria (greater than 3.5 g/d) alone does not warrant use of immunosuppressive treatment because such patients can achieve remission of proteinuria after treatment with DAAs.” Still, if other associated complications — such as anasarca, thromboembolic disease, or severe hypoalbuminemia — are present, then immunosuppressive therapy may be warranted, with rituximab remaining the preferred first-line agent.
More Work Is Needed
Dr. Awan and colleagues concluded the guideline by highlighting areas of unmet need, and how filling these knowledge gaps could lead to additional guideline updates.
“Future studies of kidney donations from HCV-positive donors to HCV-negative recipients are needed to refine and clarify the timing of initiation and duration of DAA therapy and to assess long-term outcomes associated with this practice,” they wrote. “Also, randomized controlled trials are needed to determine which patients with HCV-associated kidney disease can be treated with DAA therapy alone versus in combination with immunosuppression and plasma exchange. KDIGO will assess the currency of its recommendations and the need to update them in the next 3 years.”
The guideline was funded by KDIGO. The investigators disclosed relationships with GSK, Gilead, Intercept, Novo Nordisk, and others. Dr. Rastogi and Dr. Debes had no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE