Clinical Endocrinology News

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

The Environmental Protection Agency is proposing a new rule that would greatly limit the concentration of endocrine-disrupting “forever” chemicals in drinking water. 

The EPA on Tuesday announced the proposed National Primary Drinking Water Regulation (NPDWR) for six polyfluoroalkyl substances, more commonly known as PFAS, which are human-made chemicals used as oil and water repellents and coatings for common products including cookware, carpets, and textiles. Such substances are also widely used in cosmetics and food packaging.

curtoicurto/Getty Images

The Endocrine Society, which represents more than 18,000 doctors who treat hormone disorders, says it fully supports the new EPA proposal. It explains that these substances, also known as endocrine-disrupting chemicals, “do not break down when they are released into the environment, and they continue to accumulate over time. They pose health dangers at incredibly low levels and have been linked to endocrine disorders such as cancer, thyroid disruption, and reproductive difficulties.”

“This is the first time the government has regulated a new chemical in drinking water in more than 30 years,” the society notes, adding, this “will require major water treatment upgrades at utilities across the country.”

Robert F. Powelson, president and CEO of the National Association of Water Companies, says addressing the PFAS in the nation’s water supply will cost “billions of dollars.”

“It’s a burden that under the current structure will disproportionately fall on water and wastewater customers in small communities and low-income families,” Mr. Powelson says in a statement. He says the onus should instead fall on “the polluters” – those who manufacture and use PFAS chemicals, who “should be held directly responsible for the clean-up costs.” 

Although the EPA is proposing a health-based maximum contaminant level goal of zero for these chemicals in drinking water, it acknowledges that this is unenforceable and so has set what it considers an enforceable level, or maximum contaminant level (MCL), of 4 parts per trillion for two of the PFAS, perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS). 

A different standard has been proposed for the remaining four chemicals: perfluorononanoic acid (PFNA) and hexafluoropropylene oxide dimer acid (HFPO-DA) – known together as GenX chemicals – perfluorohexane sulfonic acid (PFHxS), and perfluorobutane sulfonic acid (PFBS).

Officials from the EPA told The Washington Post that these proposed limits would be as strong or stronger than limits from about a dozen states that have set their own drinking water standards in recent years. 

“The experts here felt this was the level of stringency required to protect public health, and that the law would allow for us,” EPA Administrator Michael Regan told the newspaper. “This is a transformative action that we’re taking.”

The EPA is requesting public comment on the proposed regulation and will hold a public hearing on May 4, which members of the public can register to attend and comment on the rule proposal. The last day to register is April 28. 

The EPA wants to finalize regulation by the end of 2023, although delays are common on new rules. 

If it is fully implemented, “the rule will prevent thousands of deaths and reduce tens of thousands of serious PFAS-attributable illnesses,” the EPA statement says.

A version of this article first appeared on Medscape.com.

A hybrid closed-loop automated insulin delivery system improved time-in-range for blood glucose, compared with standard care, for children with type 1 diabetes in a 13-week trial.

The hybrid closed-loop system, also called automated insulin delivery or artificial pancreas, was composed of a t:slim X2 insulin pump, a Dexcom G6 continuous glucose monitor (CGM), and Control-IQ technology system algorithm software (Tandem Diabetes Care). The system was approved in the United States in 2018 for adults and children as young as 6 years.

Type 1 diabetes treatment is particularly challenging in children younger than 6 because of their small insulin dosing requirements and unpredictable eating and activity habits, lead author R. Paul Wadwa, MD, of the Barbara Davis Center for Diabetes, University of Colorado at Denver, Aurora, and colleagues wrote.

Thus far in the United States, only the Medtronic MiniMed 770G and the Omnipod 5 automated insulin delivery systems are approved for children as young as 2 years, they noted.

In the current study of 102 children with type 1 diabetes aged at least 2 years but younger than 6 years, time-in-range over 13 weeks was higher for those randomized to the hybrid closed-loop system, compared with standard of care; the latter included either an insulin pump or multiple daily injections plus a separate Dexcom G6 CGM.

The hybrid closed-loop system added an average of about 3 hours in ideal blood glucose range over the 13 weeks, compared with no change with standard care.

Moreover, the trial was conducted during the COVID-19 pandemic, necessitating virtual care for most of the study participants. As a result, more than 80% of the training on use of the system and over 90% of all the visits were conducted virtually.

“Successful use of the closed-loop system under these conditions is an important finding that could affect the approach to initiating and monitoring the use of the closed-loop system and expand the use of such systems, particularly in patients living in areas without an endocrinologist but with reliable internet access,” the investigators wrote.

Their findings were published online in the New England Journal of Medicine.

“These results suggest that, in very young children, closed-loop systems are superior to standard care with respect to glucose control,” Daniela Bruttomesso, MD, PhD, of the University of Padua (Italy) wrote in an accompanying editorial.

“Moreover, they show that the closed-loop system can be started remotely in children in this age range, with results that are similar to those obtained when parents or guardians receive face-to-face education about the use of these systems. The closed-loop system used in this trial appeared to be safe and effective.”

Dr. Bruttomesso added: “Although the results were solid, the trial period was only 13 weeks, and there were more unscheduled contacts in the closed-loop group than in the standard care group. In addition, the authors compared a closed-loop system with standard care, rather than in-person initiation of a closed-loop system with remote initiation.”
 

More time-in-range, no hypoglycemia with automated system

The 102 children were enrolled in the trial between April 28, 2021, and Jan. 13, 2022, at three different U.S. study sites; 68 children were randomized to the closed-loop system and 34 children to standard care. All but one participant completed the 13-week study.

Both groups had virtual or in-person trial visits at 2, 6, and 13 weeks after randomization, and telephone contact at 1 and 10 weeks. Training was virtual for 55 of the 68 children in the closed-loop group (81%). A total of 91% of 407 study visits in the closed-loop and 96% of 204 study visits in the standard-care group were also virtual.

The mean percentage of time spent in target glucose range (70-180 mg/dL) increased from 56.9% at baseline to 69.3% at 13 weeks for the closed-loop group, compared with virtually no change, from 54.9% to 55.9%, in the standard-care group. The mean adjusted difference between the two groups was significant (P < .001).

The closed-loop group also spent significantly less time than the standard-care group with glucose levels above 250 mg/dL during the study period (8.4% vs. 15.0%; P < .001), had lower mean glucose levels (155 vs. 174 mg/dL; P < .001), and lower hemoglobin A1c (7.0% vs. 7.5%; P < .001).

However, time spent with glucose levels below 70 mg/dL (3.0% vs. 3.0%; P = .57) and below 54 mg/dL (0.6% vs. 0.5%) didn’t differ between the groups. 

There were two cases of severe hypoglycemia in the closed-loop group and one in the standard-care group. One case of diabetic ketoacidosis related to infusion set failure occurred in the closed-loop group versus none in the standard-care group.

Dr. Bruttomesso commented that a virtual approach has several advantages over in-person visits, including “a more relaxed environment, lower travel costs, and greater ease of contact with clinicians.”

At the same time, though, “patient preferences, possible legal issues, and accessibility to technology ... are all important considerations in choosing the most appropriate way to communicate with patients at the initiation of a closed-loop system or during routine follow-up.” The families of the patients in this trial had above-average incomes, she pointed out.

Ultimately, she said, “A mix of face-to-face visits and virtual clinic meetings may become routine in the management of diabetes in young children.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadwa reported receiving grants/contracts from Beta Bionics, Dexcom, Eli Lilly, and MannKind, travel fees from Eli Lilly, and lecture fees from Tandem Diabetes Care, and serves as a consultant for Dexcom. Dr. Bruttomesso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A hybrid closed-loop automated insulin delivery system improved time-in-range for blood glucose, compared with standard care, for children with type 1 diabetes in a 13-week trial.

The hybrid closed-loop system, also called automated insulin delivery or artificial pancreas, was composed of a t:slim X2 insulin pump, a Dexcom G6 continuous glucose monitor (CGM), and Control-IQ technology system algorithm software (Tandem Diabetes Care). The system was approved in the United States in 2018 for adults and children as young as 6 years.

Type 1 diabetes treatment is particularly challenging in children younger than 6 because of their small insulin dosing requirements and unpredictable eating and activity habits, lead author R. Paul Wadwa, MD, of the Barbara Davis Center for Diabetes, University of Colorado at Denver, Aurora, and colleagues wrote.

Thus far in the United States, only the Medtronic MiniMed 770G and the Omnipod 5 automated insulin delivery systems are approved for children as young as 2 years, they noted.

In the current study of 102 children with type 1 diabetes aged at least 2 years but younger than 6 years, time-in-range over 13 weeks was higher for those randomized to the hybrid closed-loop system, compared with standard of care; the latter included either an insulin pump or multiple daily injections plus a separate Dexcom G6 CGM.

The hybrid closed-loop system added an average of about 3 hours in ideal blood glucose range over the 13 weeks, compared with no change with standard care.

Moreover, the trial was conducted during the COVID-19 pandemic, necessitating virtual care for most of the study participants. As a result, more than 80% of the training on use of the system and over 90% of all the visits were conducted virtually.

“Successful use of the closed-loop system under these conditions is an important finding that could affect the approach to initiating and monitoring the use of the closed-loop system and expand the use of such systems, particularly in patients living in areas without an endocrinologist but with reliable internet access,” the investigators wrote.

Their findings were published online in the New England Journal of Medicine.

“These results suggest that, in very young children, closed-loop systems are superior to standard care with respect to glucose control,” Daniela Bruttomesso, MD, PhD, of the University of Padua (Italy) wrote in an accompanying editorial.

“Moreover, they show that the closed-loop system can be started remotely in children in this age range, with results that are similar to those obtained when parents or guardians receive face-to-face education about the use of these systems. The closed-loop system used in this trial appeared to be safe and effective.”

Dr. Bruttomesso added: “Although the results were solid, the trial period was only 13 weeks, and there were more unscheduled contacts in the closed-loop group than in the standard care group. In addition, the authors compared a closed-loop system with standard care, rather than in-person initiation of a closed-loop system with remote initiation.”
 

More time-in-range, no hypoglycemia with automated system

The 102 children were enrolled in the trial between April 28, 2021, and Jan. 13, 2022, at three different U.S. study sites; 68 children were randomized to the closed-loop system and 34 children to standard care. All but one participant completed the 13-week study.

Both groups had virtual or in-person trial visits at 2, 6, and 13 weeks after randomization, and telephone contact at 1 and 10 weeks. Training was virtual for 55 of the 68 children in the closed-loop group (81%). A total of 91% of 407 study visits in the closed-loop and 96% of 204 study visits in the standard-care group were also virtual.

The mean percentage of time spent in target glucose range (70-180 mg/dL) increased from 56.9% at baseline to 69.3% at 13 weeks for the closed-loop group, compared with virtually no change, from 54.9% to 55.9%, in the standard-care group. The mean adjusted difference between the two groups was significant (P < .001).

The closed-loop group also spent significantly less time than the standard-care group with glucose levels above 250 mg/dL during the study period (8.4% vs. 15.0%; P < .001), had lower mean glucose levels (155 vs. 174 mg/dL; P < .001), and lower hemoglobin A1c (7.0% vs. 7.5%; P < .001).

However, time spent with glucose levels below 70 mg/dL (3.0% vs. 3.0%; P = .57) and below 54 mg/dL (0.6% vs. 0.5%) didn’t differ between the groups. 

There were two cases of severe hypoglycemia in the closed-loop group and one in the standard-care group. One case of diabetic ketoacidosis related to infusion set failure occurred in the closed-loop group versus none in the standard-care group.

Dr. Bruttomesso commented that a virtual approach has several advantages over in-person visits, including “a more relaxed environment, lower travel costs, and greater ease of contact with clinicians.”

At the same time, though, “patient preferences, possible legal issues, and accessibility to technology ... are all important considerations in choosing the most appropriate way to communicate with patients at the initiation of a closed-loop system or during routine follow-up.” The families of the patients in this trial had above-average incomes, she pointed out.

Ultimately, she said, “A mix of face-to-face visits and virtual clinic meetings may become routine in the management of diabetes in young children.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadwa reported receiving grants/contracts from Beta Bionics, Dexcom, Eli Lilly, and MannKind, travel fees from Eli Lilly, and lecture fees from Tandem Diabetes Care, and serves as a consultant for Dexcom. Dr. Bruttomesso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A hybrid closed-loop automated insulin delivery system improved time-in-range for blood glucose, compared with standard care, for children with type 1 diabetes in a 13-week trial.

The hybrid closed-loop system, also called automated insulin delivery or artificial pancreas, was composed of a t:slim X2 insulin pump, a Dexcom G6 continuous glucose monitor (CGM), and Control-IQ technology system algorithm software (Tandem Diabetes Care). The system was approved in the United States in 2018 for adults and children as young as 6 years.

Type 1 diabetes treatment is particularly challenging in children younger than 6 because of their small insulin dosing requirements and unpredictable eating and activity habits, lead author R. Paul Wadwa, MD, of the Barbara Davis Center for Diabetes, University of Colorado at Denver, Aurora, and colleagues wrote.

Thus far in the United States, only the Medtronic MiniMed 770G and the Omnipod 5 automated insulin delivery systems are approved for children as young as 2 years, they noted.

In the current study of 102 children with type 1 diabetes aged at least 2 years but younger than 6 years, time-in-range over 13 weeks was higher for those randomized to the hybrid closed-loop system, compared with standard of care; the latter included either an insulin pump or multiple daily injections plus a separate Dexcom G6 CGM.

The hybrid closed-loop system added an average of about 3 hours in ideal blood glucose range over the 13 weeks, compared with no change with standard care.

Moreover, the trial was conducted during the COVID-19 pandemic, necessitating virtual care for most of the study participants. As a result, more than 80% of the training on use of the system and over 90% of all the visits were conducted virtually.

“Successful use of the closed-loop system under these conditions is an important finding that could affect the approach to initiating and monitoring the use of the closed-loop system and expand the use of such systems, particularly in patients living in areas without an endocrinologist but with reliable internet access,” the investigators wrote.

Their findings were published online in the New England Journal of Medicine.

“These results suggest that, in very young children, closed-loop systems are superior to standard care with respect to glucose control,” Daniela Bruttomesso, MD, PhD, of the University of Padua (Italy) wrote in an accompanying editorial.

“Moreover, they show that the closed-loop system can be started remotely in children in this age range, with results that are similar to those obtained when parents or guardians receive face-to-face education about the use of these systems. The closed-loop system used in this trial appeared to be safe and effective.”

Dr. Bruttomesso added: “Although the results were solid, the trial period was only 13 weeks, and there were more unscheduled contacts in the closed-loop group than in the standard care group. In addition, the authors compared a closed-loop system with standard care, rather than in-person initiation of a closed-loop system with remote initiation.”
 

More time-in-range, no hypoglycemia with automated system

The 102 children were enrolled in the trial between April 28, 2021, and Jan. 13, 2022, at three different U.S. study sites; 68 children were randomized to the closed-loop system and 34 children to standard care. All but one participant completed the 13-week study.

Both groups had virtual or in-person trial visits at 2, 6, and 13 weeks after randomization, and telephone contact at 1 and 10 weeks. Training was virtual for 55 of the 68 children in the closed-loop group (81%). A total of 91% of 407 study visits in the closed-loop and 96% of 204 study visits in the standard-care group were also virtual.

The mean percentage of time spent in target glucose range (70-180 mg/dL) increased from 56.9% at baseline to 69.3% at 13 weeks for the closed-loop group, compared with virtually no change, from 54.9% to 55.9%, in the standard-care group. The mean adjusted difference between the two groups was significant (P < .001).

The closed-loop group also spent significantly less time than the standard-care group with glucose levels above 250 mg/dL during the study period (8.4% vs. 15.0%; P < .001), had lower mean glucose levels (155 vs. 174 mg/dL; P < .001), and lower hemoglobin A1c (7.0% vs. 7.5%; P < .001).

However, time spent with glucose levels below 70 mg/dL (3.0% vs. 3.0%; P = .57) and below 54 mg/dL (0.6% vs. 0.5%) didn’t differ between the groups. 

There were two cases of severe hypoglycemia in the closed-loop group and one in the standard-care group. One case of diabetic ketoacidosis related to infusion set failure occurred in the closed-loop group versus none in the standard-care group.

Dr. Bruttomesso commented that a virtual approach has several advantages over in-person visits, including “a more relaxed environment, lower travel costs, and greater ease of contact with clinicians.”

At the same time, though, “patient preferences, possible legal issues, and accessibility to technology ... are all important considerations in choosing the most appropriate way to communicate with patients at the initiation of a closed-loop system or during routine follow-up.” The families of the patients in this trial had above-average incomes, she pointed out.

Ultimately, she said, “A mix of face-to-face visits and virtual clinic meetings may become routine in the management of diabetes in young children.”

The study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases. Dr. Wadwa reported receiving grants/contracts from Beta Bionics, Dexcom, Eli Lilly, and MannKind, travel fees from Eli Lilly, and lecture fees from Tandem Diabetes Care, and serves as a consultant for Dexcom. Dr. Bruttomesso reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians are admired for their sacrifice and dedication. Yet beneath the surface lies a painful, quiet reality: Physicians take their lives more than any other professional, reported at 40 per 100,000. Nearly one doctor dies by suicide every day.

The Physicians Foundation says that 55% of physicians know a doctor who considered, attempted, or died by suicide. Doctor’s Burden: Medscape Physician Suicide Report 2023 asked more than 9,000 doctors if they had suicidal thoughts. Nine percent of male physicians and 11% of female physicians said yes.
 

Why do so many doctors take their own lives?

“It’s not a new phenomenon,” says Rajnish Jaiswal, MD, associate chief of emergency medicine at NYC H+H Metropolitan Hospital and assistant professor of emergency medicine at New York Medical College. “There was a paper 150 years ago, published in England, which commented on the high rates of physician suicides compared to other professionals, and that trend has continued.”

Dr. Jaiswal says that the feeling in the physician community is that the numbers are even higher than what’s reported, unfortunately, which is an opinion echoed by other doctors this news organization spoke with for this story.
 

A perfect storm

Jodie Eckleberry-Hunt, PhD, a board-certified health psychologist, executive coach, and author, says the most significant culprit historically may be a rigid mindset that many physicians have. “There’s black and white, there’s a right answer and a wrong answer, there’s good and bad, and some physicians have a really hard time flexing,” she says.

Psychological flexibility underlies resilience. Dr. Eckleberry-Hunt says, “Think about your bounce factor and how that resilience is protective. Life isn’t always going to go well. You have to be able to flex and bounce, and some physicians (not all of them, of course) tend to be lower on cognitive flexibility.”

Brad Fern, coach and psychotherapist at Fern Executive and Physician Consulting, Minneapolis, says he uses two analogies that help when he works with physicians. One is the evil twins, and the other is the pressure cooker.

Mr. Fern says that the evil twins are silence and isolation and that several professions, including physicians, fall prey to these. To put any dent in suicidal ideations and suicide, Mr. Fern says, these must be addressed.

“Physicians tend not to talk about what’s bothering them, and that’s for many different reasons. They disproportionally tend to be great at helping other people but not great at receiving help themselves.”

On top of that, there’s a pressure cooker where they work. Mr. Fern doesn’t think anyone would argue that the health care system in the United States is not dysfunctional, at least to some degree. He says that this dysfunction acts like the physicians’ pressure cooker.

Add in circumstances, cultures, and day-to-day issues everyone has, like relational issues, parenting issues, and mental health problems. Then, toss in an individual’s lower resiliency, the inability to receive help, and a predicament for good measure – a loss, a divorce, or financial woes, for instance, which can overwhelm. Mr. Fern says it can be a mathematical equation for suicidal ideation.
 

Is there a why?

“Some people think there’s a reason for suicide, but often, there’s a spectrum of reasons,” says Mr. Fern. He says that some physicians are trying to escape emotional pain. For others, it can be fear or a revenge thing, like, “the hell with you, I’m going to kill myself.” It can be getting attention the way teens do, as professionals have seen. Then there’s the organic component, like brain trauma, brain imbalance, depression, anxiety, or bipolar disorder. And finally, a drug or alcohol issue.

“But the reason why physician suicide is elevated, I think, is because there’s this ethos around being silent and, ‘I’m going to listen to and solve everyone else’s problems, but I’m not going to reach out and get help for my own,’ ” says Mr. Fern. “If you take advantage of mental health services, you’re implying that you’re mentally ill. And most physicians aren’t going to do that.”

On the positive side, Dr. Eckleberry-Hunt says that she sees many younger physicians discussing trauma. As a result, they’re more open to receiving help than previous generations. She speculates whether physicians have always had trauma from their past and whether current-day issues are now triggering it or whether they have more trauma these days. “Are they talking about it more, or is it experienced more?”
 

The failure of the system

The building blocks for physician suicide may have been there from the beginning. “From your first day of medical school and throughout your career, there was a very rigid system in place that is quite unforgiving, is quite stressful, and demands a lot,” says Dr. Jaiswal. And it’s within this system that physicians must operate.

“You have all the corporations, entities, organizations, [and] medical societies talking about physician wellness, burnout, and suicide, but the reality is it’s not making that much of a difference,” he says.

In her report, “What I’ve Learned From 1,710 Doctor Suicides,” Pamelia Wible, MD, who runs a physician suicide helpline that physicians can email and get an immediate callback, likens the current system to assembly line medicine.

Dr. Eckleberry-Hunt thinks the message has been bungled in health care. Everyone discusses burnout, meditation, self-care, and other essential constructs. “But we don’t deal with the root cause [of suicide]. Instead, we teach you soothing strategies.”

Further, Dr. Jaiswal says that not all physicians who commit suicide experience burnout or are experiencing burnout and that the vast majority of physicians who experience burnout don’t have suicidal ideation. “In the sense, that ‘let’s address physician burnout and that will hopefully translate to a reduced number of physician suicides’ – there is a very tenuous argument to be made for that because that is just one aspect in this complex system,” he says.
 

We need more than just lip service on suicide

Overall, the experts interviewed for this article acknowledged that the system is at least talking about physician suicide, which is a big first step. However, most agree that where big health entities go wrong is that they set up wellness or mental health programs, they implement a wellness officer, they write up talking points for physicians who need mental health care to get that care, and they think they’ve done their job, that they’ve done what’s required to address the problem.

But Dr. Jaiswal thinks these are often mostly public-relations rebuttals. Mr. Fern suggests, “It’s a show that’s not effective.” And Dr. Eckleberry-Hunt says that “even if you had a legit, well-funded well-being program for health care providers, you would still have a baseline rate of physician suicide, and that gets down to having drug and alcohol education and talking about having a system for physicians to access that doesn’t come along with insurance billing” – one that doesn’t create a paper trail and follow physician licensure and job applications for the rest of their career; one that doesn’t associate their mental health care with their work institution; one that offers confidentiality.

“For most folks, there is still a big distrust in the system. As physicians, very few of them feel that the system that they’re operating in has their best interest at heart. And that is why very few physicians will self-report any mental health issues, depression, or even ideation to colleagues, superiors, or managers,” says Dr. Jaiswal. Many more feel skeptical about the confidentiality of the programs in place.

The experts acknowledge that many people are trying to work on this and bring about change on multiple levels – grassroots, department levels, state, and federal. “But I think the biggest thing that the system has to do is earn back the trust of the physician,” Dr. Jaiswal adds.

“Physician suicide is a very visible problem in a very broken system. So, it’ll be very difficult in isolation to treat it without making any systemic changes, because that’s happening right now, and it’s not working,” says Dr. Jaiswal.

“The thing that I am most hopeful about is that I am seeing an influx of younger physicians who seek me out, and granted, their training programs tell them to come and see me, but they are ready and willing to talk about their mental health separate from work. They’re not coming in saying, ‘Here are all the people who I blame.’ They’re saying, ‘These are my struggles, and I want to be a better, happier physician,’ ” says Dr. Eckleberry-Hunt.

A version of this article originally appeared on Medscape.com.

Physicians are admired for their sacrifice and dedication. Yet beneath the surface lies a painful, quiet reality: Physicians take their lives more than any other professional, reported at 40 per 100,000. Nearly one doctor dies by suicide every day.

The Physicians Foundation says that 55% of physicians know a doctor who considered, attempted, or died by suicide. Doctor’s Burden: Medscape Physician Suicide Report 2023 asked more than 9,000 doctors if they had suicidal thoughts. Nine percent of male physicians and 11% of female physicians said yes.
 

Why do so many doctors take their own lives?

“It’s not a new phenomenon,” says Rajnish Jaiswal, MD, associate chief of emergency medicine at NYC H+H Metropolitan Hospital and assistant professor of emergency medicine at New York Medical College. “There was a paper 150 years ago, published in England, which commented on the high rates of physician suicides compared to other professionals, and that trend has continued.”

Dr. Jaiswal says that the feeling in the physician community is that the numbers are even higher than what’s reported, unfortunately, which is an opinion echoed by other doctors this news organization spoke with for this story.
 

A perfect storm

Jodie Eckleberry-Hunt, PhD, a board-certified health psychologist, executive coach, and author, says the most significant culprit historically may be a rigid mindset that many physicians have. “There’s black and white, there’s a right answer and a wrong answer, there’s good and bad, and some physicians have a really hard time flexing,” she says.

Psychological flexibility underlies resilience. Dr. Eckleberry-Hunt says, “Think about your bounce factor and how that resilience is protective. Life isn’t always going to go well. You have to be able to flex and bounce, and some physicians (not all of them, of course) tend to be lower on cognitive flexibility.”

Brad Fern, coach and psychotherapist at Fern Executive and Physician Consulting, Minneapolis, says he uses two analogies that help when he works with physicians. One is the evil twins, and the other is the pressure cooker.

Mr. Fern says that the evil twins are silence and isolation and that several professions, including physicians, fall prey to these. To put any dent in suicidal ideations and suicide, Mr. Fern says, these must be addressed.

“Physicians tend not to talk about what’s bothering them, and that’s for many different reasons. They disproportionally tend to be great at helping other people but not great at receiving help themselves.”

On top of that, there’s a pressure cooker where they work. Mr. Fern doesn’t think anyone would argue that the health care system in the United States is not dysfunctional, at least to some degree. He says that this dysfunction acts like the physicians’ pressure cooker.

Add in circumstances, cultures, and day-to-day issues everyone has, like relational issues, parenting issues, and mental health problems. Then, toss in an individual’s lower resiliency, the inability to receive help, and a predicament for good measure – a loss, a divorce, or financial woes, for instance, which can overwhelm. Mr. Fern says it can be a mathematical equation for suicidal ideation.
 

Is there a why?

“Some people think there’s a reason for suicide, but often, there’s a spectrum of reasons,” says Mr. Fern. He says that some physicians are trying to escape emotional pain. For others, it can be fear or a revenge thing, like, “the hell with you, I’m going to kill myself.” It can be getting attention the way teens do, as professionals have seen. Then there’s the organic component, like brain trauma, brain imbalance, depression, anxiety, or bipolar disorder. And finally, a drug or alcohol issue.

“But the reason why physician suicide is elevated, I think, is because there’s this ethos around being silent and, ‘I’m going to listen to and solve everyone else’s problems, but I’m not going to reach out and get help for my own,’ ” says Mr. Fern. “If you take advantage of mental health services, you’re implying that you’re mentally ill. And most physicians aren’t going to do that.”

On the positive side, Dr. Eckleberry-Hunt says that she sees many younger physicians discussing trauma. As a result, they’re more open to receiving help than previous generations. She speculates whether physicians have always had trauma from their past and whether current-day issues are now triggering it or whether they have more trauma these days. “Are they talking about it more, or is it experienced more?”
 

The failure of the system

The building blocks for physician suicide may have been there from the beginning. “From your first day of medical school and throughout your career, there was a very rigid system in place that is quite unforgiving, is quite stressful, and demands a lot,” says Dr. Jaiswal. And it’s within this system that physicians must operate.

“You have all the corporations, entities, organizations, [and] medical societies talking about physician wellness, burnout, and suicide, but the reality is it’s not making that much of a difference,” he says.

In her report, “What I’ve Learned From 1,710 Doctor Suicides,” Pamelia Wible, MD, who runs a physician suicide helpline that physicians can email and get an immediate callback, likens the current system to assembly line medicine.

Dr. Eckleberry-Hunt thinks the message has been bungled in health care. Everyone discusses burnout, meditation, self-care, and other essential constructs. “But we don’t deal with the root cause [of suicide]. Instead, we teach you soothing strategies.”

Further, Dr. Jaiswal says that not all physicians who commit suicide experience burnout or are experiencing burnout and that the vast majority of physicians who experience burnout don’t have suicidal ideation. “In the sense, that ‘let’s address physician burnout and that will hopefully translate to a reduced number of physician suicides’ – there is a very tenuous argument to be made for that because that is just one aspect in this complex system,” he says.
 

We need more than just lip service on suicide

Overall, the experts interviewed for this article acknowledged that the system is at least talking about physician suicide, which is a big first step. However, most agree that where big health entities go wrong is that they set up wellness or mental health programs, they implement a wellness officer, they write up talking points for physicians who need mental health care to get that care, and they think they’ve done their job, that they’ve done what’s required to address the problem.

But Dr. Jaiswal thinks these are often mostly public-relations rebuttals. Mr. Fern suggests, “It’s a show that’s not effective.” And Dr. Eckleberry-Hunt says that “even if you had a legit, well-funded well-being program for health care providers, you would still have a baseline rate of physician suicide, and that gets down to having drug and alcohol education and talking about having a system for physicians to access that doesn’t come along with insurance billing” – one that doesn’t create a paper trail and follow physician licensure and job applications for the rest of their career; one that doesn’t associate their mental health care with their work institution; one that offers confidentiality.

“For most folks, there is still a big distrust in the system. As physicians, very few of them feel that the system that they’re operating in has their best interest at heart. And that is why very few physicians will self-report any mental health issues, depression, or even ideation to colleagues, superiors, or managers,” says Dr. Jaiswal. Many more feel skeptical about the confidentiality of the programs in place.

The experts acknowledge that many people are trying to work on this and bring about change on multiple levels – grassroots, department levels, state, and federal. “But I think the biggest thing that the system has to do is earn back the trust of the physician,” Dr. Jaiswal adds.

“Physician suicide is a very visible problem in a very broken system. So, it’ll be very difficult in isolation to treat it without making any systemic changes, because that’s happening right now, and it’s not working,” says Dr. Jaiswal.

“The thing that I am most hopeful about is that I am seeing an influx of younger physicians who seek me out, and granted, their training programs tell them to come and see me, but they are ready and willing to talk about their mental health separate from work. They’re not coming in saying, ‘Here are all the people who I blame.’ They’re saying, ‘These are my struggles, and I want to be a better, happier physician,’ ” says Dr. Eckleberry-Hunt.

A version of this article originally appeared on Medscape.com.

Physicians are admired for their sacrifice and dedication. Yet beneath the surface lies a painful, quiet reality: Physicians take their lives more than any other professional, reported at 40 per 100,000. Nearly one doctor dies by suicide every day.

The Physicians Foundation says that 55% of physicians know a doctor who considered, attempted, or died by suicide. Doctor’s Burden: Medscape Physician Suicide Report 2023 asked more than 9,000 doctors if they had suicidal thoughts. Nine percent of male physicians and 11% of female physicians said yes.
 

Why do so many doctors take their own lives?

“It’s not a new phenomenon,” says Rajnish Jaiswal, MD, associate chief of emergency medicine at NYC H+H Metropolitan Hospital and assistant professor of emergency medicine at New York Medical College. “There was a paper 150 years ago, published in England, which commented on the high rates of physician suicides compared to other professionals, and that trend has continued.”

Dr. Jaiswal says that the feeling in the physician community is that the numbers are even higher than what’s reported, unfortunately, which is an opinion echoed by other doctors this news organization spoke with for this story.
 

A perfect storm

Jodie Eckleberry-Hunt, PhD, a board-certified health psychologist, executive coach, and author, says the most significant culprit historically may be a rigid mindset that many physicians have. “There’s black and white, there’s a right answer and a wrong answer, there’s good and bad, and some physicians have a really hard time flexing,” she says.

Psychological flexibility underlies resilience. Dr. Eckleberry-Hunt says, “Think about your bounce factor and how that resilience is protective. Life isn’t always going to go well. You have to be able to flex and bounce, and some physicians (not all of them, of course) tend to be lower on cognitive flexibility.”

Brad Fern, coach and psychotherapist at Fern Executive and Physician Consulting, Minneapolis, says he uses two analogies that help when he works with physicians. One is the evil twins, and the other is the pressure cooker.

Mr. Fern says that the evil twins are silence and isolation and that several professions, including physicians, fall prey to these. To put any dent in suicidal ideations and suicide, Mr. Fern says, these must be addressed.

“Physicians tend not to talk about what’s bothering them, and that’s for many different reasons. They disproportionally tend to be great at helping other people but not great at receiving help themselves.”

On top of that, there’s a pressure cooker where they work. Mr. Fern doesn’t think anyone would argue that the health care system in the United States is not dysfunctional, at least to some degree. He says that this dysfunction acts like the physicians’ pressure cooker.

Add in circumstances, cultures, and day-to-day issues everyone has, like relational issues, parenting issues, and mental health problems. Then, toss in an individual’s lower resiliency, the inability to receive help, and a predicament for good measure – a loss, a divorce, or financial woes, for instance, which can overwhelm. Mr. Fern says it can be a mathematical equation for suicidal ideation.
 

Is there a why?

“Some people think there’s a reason for suicide, but often, there’s a spectrum of reasons,” says Mr. Fern. He says that some physicians are trying to escape emotional pain. For others, it can be fear or a revenge thing, like, “the hell with you, I’m going to kill myself.” It can be getting attention the way teens do, as professionals have seen. Then there’s the organic component, like brain trauma, brain imbalance, depression, anxiety, or bipolar disorder. And finally, a drug or alcohol issue.

“But the reason why physician suicide is elevated, I think, is because there’s this ethos around being silent and, ‘I’m going to listen to and solve everyone else’s problems, but I’m not going to reach out and get help for my own,’ ” says Mr. Fern. “If you take advantage of mental health services, you’re implying that you’re mentally ill. And most physicians aren’t going to do that.”

On the positive side, Dr. Eckleberry-Hunt says that she sees many younger physicians discussing trauma. As a result, they’re more open to receiving help than previous generations. She speculates whether physicians have always had trauma from their past and whether current-day issues are now triggering it or whether they have more trauma these days. “Are they talking about it more, or is it experienced more?”
 

The failure of the system

The building blocks for physician suicide may have been there from the beginning. “From your first day of medical school and throughout your career, there was a very rigid system in place that is quite unforgiving, is quite stressful, and demands a lot,” says Dr. Jaiswal. And it’s within this system that physicians must operate.

“You have all the corporations, entities, organizations, [and] medical societies talking about physician wellness, burnout, and suicide, but the reality is it’s not making that much of a difference,” he says.

In her report, “What I’ve Learned From 1,710 Doctor Suicides,” Pamelia Wible, MD, who runs a physician suicide helpline that physicians can email and get an immediate callback, likens the current system to assembly line medicine.

Dr. Eckleberry-Hunt thinks the message has been bungled in health care. Everyone discusses burnout, meditation, self-care, and other essential constructs. “But we don’t deal with the root cause [of suicide]. Instead, we teach you soothing strategies.”

Further, Dr. Jaiswal says that not all physicians who commit suicide experience burnout or are experiencing burnout and that the vast majority of physicians who experience burnout don’t have suicidal ideation. “In the sense, that ‘let’s address physician burnout and that will hopefully translate to a reduced number of physician suicides’ – there is a very tenuous argument to be made for that because that is just one aspect in this complex system,” he says.
 

We need more than just lip service on suicide

Overall, the experts interviewed for this article acknowledged that the system is at least talking about physician suicide, which is a big first step. However, most agree that where big health entities go wrong is that they set up wellness or mental health programs, they implement a wellness officer, they write up talking points for physicians who need mental health care to get that care, and they think they’ve done their job, that they’ve done what’s required to address the problem.

But Dr. Jaiswal thinks these are often mostly public-relations rebuttals. Mr. Fern suggests, “It’s a show that’s not effective.” And Dr. Eckleberry-Hunt says that “even if you had a legit, well-funded well-being program for health care providers, you would still have a baseline rate of physician suicide, and that gets down to having drug and alcohol education and talking about having a system for physicians to access that doesn’t come along with insurance billing” – one that doesn’t create a paper trail and follow physician licensure and job applications for the rest of their career; one that doesn’t associate their mental health care with their work institution; one that offers confidentiality.

“For most folks, there is still a big distrust in the system. As physicians, very few of them feel that the system that they’re operating in has their best interest at heart. And that is why very few physicians will self-report any mental health issues, depression, or even ideation to colleagues, superiors, or managers,” says Dr. Jaiswal. Many more feel skeptical about the confidentiality of the programs in place.

The experts acknowledge that many people are trying to work on this and bring about change on multiple levels – grassroots, department levels, state, and federal. “But I think the biggest thing that the system has to do is earn back the trust of the physician,” Dr. Jaiswal adds.

“Physician suicide is a very visible problem in a very broken system. So, it’ll be very difficult in isolation to treat it without making any systemic changes, because that’s happening right now, and it’s not working,” says Dr. Jaiswal.

“The thing that I am most hopeful about is that I am seeing an influx of younger physicians who seek me out, and granted, their training programs tell them to come and see me, but they are ready and willing to talk about their mental health separate from work. They’re not coming in saying, ‘Here are all the people who I blame.’ They’re saying, ‘These are my struggles, and I want to be a better, happier physician,’ ” says Dr. Eckleberry-Hunt.

A version of this article originally appeared on Medscape.com.

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

A version of this article first appeared on Medscape.com.

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

A version of this article first appeared on Medscape.com.

A new oral formulation of a PCSK9-inhibiting, cholesterol-lowering drug in development by Merck has shown encouraging results in a phase 2 study.

The study was presented by Christie Ballantyne, MD, Baylor College of Medicine, Houston, at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.

Mitchel L. Zoler/MDedge News

“In this diverse population of hypercholesterolemic patients, all doses of MK-0616 showed superior reduction of LDL vs. placebo up to a 60.9% placebo-adjusted reduction from baseline to week 8, which was consistent across subgroups,” Dr. Ballantyne reported.

“Reduction in ApoB and non-HDL cholesterol were consistent with that of LDL cholesterol, with up to a 51.8% reduction in ApoB and a 55.8% reduction in non-HDL,” he noted.  

He added that the drug was well tolerated with no difference in adverse events across the treatment groups, compared with placebo.

“These data support the further development of MK-0616, an oral PCSK9 inhibitor that may improve access to effective LDL-cholesterol lowering therapies and improve attainment of guideline-recommended LDL goals aimed at reducing cardiovascular risk,” Dr. Ballantyne concluded. “The results are encouraging for a phase 3 program that is now being designed.”

He explained that elevated LDL is a primary causative factor for atherosclerotic cardiovascular disease (ASCVD), and despite effective treatments (statins), a large proportion of patients fail to achieve guideline-recommended LDL levels. Injectable treatments targeting PCSK9 have demonstrated large reductions in LDL and decreased risk of ASCVD events, but access barriers and need for repeat injections have led to poor adoption. An oral PCSK9 inhibitor may widen access and improve attainment of guideline-recommended treatment goals.

Dr. Ballantyne described the new drug, MK-0616, as a “macrocyclic peptide that can bind PCSK9 with monoclonal antibody-like affinity at 1/100th of the molecular weight.”

The current phase 2 study included 381 adult patients (49% female; median age 62 years) with a wide range of ASCVD risk. Average LDL-C level was 119.5 mg/dL at baseline. Around 40% of patients were not taking statins, 35% were on low- to moderate-intensity statin therapy, and 26% were on high-intensity statin therapy.

They were randomly assigned to four different doses of MK-0616 (6, 12, 18, or 30 mg once daily) or matching placebo.

Results showed that all doses of MK-0616 demonstrated statistically significant differences in percentage change in LDL-C from baseline to week 8 vs. placebo: –41.2% (6 mg), –55.7% (12 mg), –59.1% (18 mg), and –60.9% (30 mg).

The mean percentage changes in ApoB from baseline vs. placebo were –32.8%, –45.8%, –48.7%, and 51.8% for the four escalating doses of the drug. And non-HDL cholesterol changes were –35.9%, –50.5%, –53.2%, and –55.8% respectively.

The proportion of participants at protocol-defined goals for LDL reduction was 80.5%, 85.5%, 90.8%, and 90.8% with MK-0616 at the 6-mg, 12-mg, 18-mg, and 30-mg doses, compared with 9.3% with placebo.

Dr. Ballantyne reported that the efficacy looked similar in all subgroups, and regardless of baseline therapy. 

“This was a dose-finding study, which will help select a dose to be taken forward in larger studies, and it looks from these results as though you get most of the efficacy by 12 mg,” he added.  

Adverse events occurred in a proportion of participants in the MK-0616 groups (39.5% to 43.4%) similar to that of placebo (44.0%), and discontinuations as a result of adverse events occurred in two or fewer participants in any treatment group.
 

‘Super exciting’

Putting the results of his study into perspective at an ACC press conference, Rhonda Cooper-DeHoff, PharmD, associate professor in the department of pharmacotherapy and translational research at the University of Florida in Gainesville, commented.

Mitchel L. Zoler/MDedge News

“For the last quarter of a century we have had statins available to treat elevated LDL and atherosclerosis and despite that we have many patients who refuse to take statins or are afraid to take statins,” she said. “This is not about cost as the statins are all available generically now. But many patients claim to be intolerant or unresponsive.”

She noted that in 2015/2016 the first injectable PCSK9 inhibitors became available “which really were very exciting molecules, but they have a high cost and access issues, and patients often do not like injections so there are still a lot of issues.”

Dr. Cooper-DeHoff pointed out that this oral PCSK9 inhibitor seems to be as effective at lowering LDL as the injectable products regardless of whether statins are on board or not, which she said was “super exciting.”

She added: “We are all going to be waiting excitedly for the outcome data with this oral PCSK9 inhibitor.”

She also noted that another study (CLEAR Outcomes) presented at the ACC meeting showed good lipid-lowering results and a reduction in cardiovascular outcomes in statin-intolerant patients with another oral lipid lowering drug, bempedoic acid (Nexletol).

She said the two oral drugs promised a “very bright for the future for LDL lowering and the treatment of atherosclerosis in our patients,” adding that “we are now really chipping away at the barriers to achieving the holy grail of guideline-directed LDL lowering to prevent hard outcomes.”

The results were published online in the Journal of the American College of Cardiology at the time of presentation. 

This study was funded by Merck. Dr. Ballantyne has received grant/research support through his institution from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostics and has been a consultant for 89Bio, Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, AstraZeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostics.

A version of this article first appeared on Medscape.com.

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

A version of this article first appeared on Medscape.com.

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

A version of this article first appeared on Medscape.com.

High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.

Courtesy National Cancer Institute

The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.

Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.

However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.

Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
 

Ultraprocessed food intake higher in the U.S. than in Europe

The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.

They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.

In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.

In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.

Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.

Servings per day were then used to determine individual UPF intake.

Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.

The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.

Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.

Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.

The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.

In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.

Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.

They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
 

Ideal is to have access to minimally processed foods

The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”

A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.

Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.

Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”

The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.

Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”

Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
 

Using GLP-1 receptor agonists for obesity

We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.

Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.

The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.

The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.

In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.

The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
 

Why the concern about thyroid cancer?

Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.

Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.

Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.

Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.

Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.

And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.

Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.

An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.

While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.

No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.

Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
 

How to advise our patients and respond to the EMR messages

The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.

It’s prudent to advise patients that if they have a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2, in particular, they should avoid using this class of medication. Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.

A version of this article first appeared on Medscape.com.

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Do android therapists dream of electric employees?

Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.

University of Cambridge

Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.

Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.

The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.

People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.

That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.

Birthing experience is all in the mindset

Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.

Birth.

Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.

joruba/Thinkstock

The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).

Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.

Apparently, yes.

“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”

The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.

Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?

Becoming a parent is going to create a psychological shift, no matter how you slice it.

Giant inflatable colon reported in Utah

Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.

Hiroshi Watanabe/Getty Images

The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.

Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.

Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.

Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:

• Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
• Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Higher blood caffeine levels appear to reduce the risks for both adiposity and type 2 diabetes, the results of a new study suggest.

Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.

In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.

The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”

Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.

The work was published online March 14 in BMJ Medicine.

“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.

“It does not, however, prove cause and effect.”

The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”

Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”

“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.

Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.

Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m² in BMI (P < .001).

For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).

Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).

Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).

Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.

They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).

The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.

“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”

The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.

Yet diagnostic uncertainty is an inevitable part of medicine.

“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.

By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.

“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.

To begin to answer these questions, Dr. Schiff and colleagues developed four clinical scenarios carrying unclear diagnoses and asked primary care physicians how they would convey the lack of clarity to patients. The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.

For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.

Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.

• The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
• Next steps – lab tests, return visits, etc.
• Expected time frame for patient’s improvement and recovery.
• Full disclosure of the limitations of the physical examination or any lab tests.
• Ways to contact the physician going forward.
• Patient insights on their experience and reaction to what they just heard.

The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.

“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.

Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.

Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.

“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.

“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia. 

Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty. 

“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.

Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.

The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.

In the United States, the Centers for Disease Control and Prevention estimates that nearly one in five children have obesity. Since the 1980s, the number of children with obesity has been increasing, with each generation reaching higher rates and greater weights at earlier ages. Even with extensive efforts from parents, clinicians, educators, and policymakers to limit the excessive weight gain among children, the number of obesity and severe obesity diagnoses keeps rising.

In response to this critical public health challenge, the American Academy of Pediatrics (AAP) introduced new clinical practice guidelines for the evaluation and management of obesity in children and adolescents. Developed by an expert panel, the new AAP guidelines present a departure in the conceptualization of obesity, recognizing the role that social determinants of health play in contributing to excessive weight gain.

As a community health researcher who investigates disparities in childhood obesity, I applaud the paradigm shift from the AAP. I specifically endorse the recognition that obesity is a very serious metabolic disease that won’t go away unless we introduce systemic changes and effective treatments.

However, I, like so many of my colleagues and anyone aware of the access barriers to the recommended treatments, worry about the consequences that the new guidelines will have in the context of current and future health disparities.

A recent study, published in Pediatrics, showed that childhood obesity disparities are widening. Younger generations of children are reaching higher weights at younger ages. These alarming trends are greater among Black children and children growing up with the greatest socioeconomic disadvantages. The new AAP guidelines – even while driven by good intentions – can exacerbate these differences and set children who are able to live healthy lives further apart from those with disproportionate obesity risks, who lack access to the treatments recommended by the AAP.

Rather than “watchful waiting,” to see if children outgrow obesity, the new guidelines call for “aggressive treatment,” as reported by this news organization. At least 26 hours of in-person intensive health behavior and lifestyle counseling and treatment are recommended for children aged 2 years old or older who meet the obesity criteria. For children aged 12 years or older, the AAP recommends complementing lifestyle counseling with pharmacotherapy. This breakthrough welcomes the use of promising antiobesity medications (for example, orlistat, Wegovy [semaglutide], Saxenda [liraglutide], Qsymia (phentermine and topiramate]) approved by the Food and Drug Administration for long-term use in children aged 12 and up. For children 13 years or older with severe obesity, bariatric surgery should be considered.
 

Will cost barriers continue to increase disparity?

The very promising semaglutide (Wegovy) is a GLP-1–based medication currently offered for about $1,000 per month. As with other chronic diseases, children should be prepared to take obesity medications for prolonged periods of time. A study conducted in adults found that when the medication is suspended, any weight loss can be regained. The costs of bariatric surgery total over $20,000.

In the U.S. health care system, at current prices, very few of the children in need of the medications or surgical treatments have access to them. Most private health insurance companies and Medicaid reject coverage for childhood obesity treatments. Barriers to treatment access are greater for Black and Hispanic children, children growing up in poverty, and children living in the U.S. South region, all of whom are more likely to develop obesity earlier in life than their White and wealthier counterparts.

The AAP recognized that a substantial time and financial commitment is required to follow the new treatment recommendations. Members of the AAP Expert Committee that developed the guidelines stated that they are “aware of the multitude of barriers to treatment that patients and their families face.”

Nevertheless, the recognition of the role of social determinants of health in the development of childhood obesity didn’t motivate the introduction of treatment options that aren’t unattainable for most U.S. families.

It’s important to step away from the conclusion that because of the price tag, at the population level, the new AAP guidelines will be inconsequential. This conclusion fails to recognize the potential harm that the guidelines may introduce. In the context of childhood obesity disparities, the new treatment recommendations probably will widen the childhood obesity prevalence gap between the haves – who will benefit from the options available to reduce childhood obesity – and the have-nots, whose obesity rates will continue with their growth.

We live in a world of the haves and have-nots. This applies to financial resources as well as obesity rates. In the long term, the optimists hope that the GLP-1 medications will become ubiquitous, generics will be developed, and insurance companies will expand coverage and grant access to most children in need of effective obesity treatment options. Until this happens, unless intentional policies are promptly introduced, childhood obesity disparities will continue to widen.

To avoid the increasing disparities, brave and intentional actions are required. A lack of attention dealt to this known problem will result in a lost opportunity for the AAP, legislators, and others in a position to help U.S. children.

Liliana Aguayo, PhD, MPH, is assistant professor, Clinical Research Track, Hubert Department of Global Health, Emory University, Atlanta. A version of this article first appeared on Medscape.com.