MDedge Endocrinology

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

VIENNA – Resolution of nonalcoholic steatohepatitis (NASH), and reduction of fibrosis on liver biopsy were achieved with the oral, thyroid hormone receptor beta-selective agonist resmetirom (Madrigal Pharmaceuticals) in patients with NASH and associated cirrhosis in a pivotal phase 3 clinical trial. The primary results of the MAESTRO-NASH (NCT03900429) trial were reported at the European Association for the Study of the Liver Congress 2023.

Both doses of resmetirom – 80 mg and 100 mg – met the primary endpoints of NASH resolution and no worsening of fibrosis on liver biopsy. The key secondary endpoint of LDL cholesterol lowering was also achieved with statistical significance. Likewise, improvement was seen in liver enzymes, and liver and spleen volumes.

In the intent-to-treat population, NASH resolution was achieved in 26% (P < .0001) in the 80-mg resmetirom group, 30% (P < .0001) in the 100-mg group, and 10% in those taking placebo. And ≥ 1-stage improvement in fibrosis with no worsening of the nonalcoholic fatty liver disease activity score (NAS) was achieved by 24% (P < .0002), 26% (P < .0001), and 14% in these groups respectively.

The investigational, liver-directed agent, designed to improve NASH by increasing hepatic fat metabolism and reducing lipotoxicity, was well tolerated overall with a favorable safety profile.

“This is an exciting time for NASH because we are at the forefront of having a drug to treat these patients, and the benefit to patients promises to be huge,” asserted Stephen Harrison, MD, principal investigator of the MAESTRO studies, gastroenterologist and hepatologist, and founder of Pinnacle Clinical Research, San Antonio, in reporting 52-week results.

“This is the first treatment to achieve meaningful effects on both primary liver biopsy endpoints – disease activity and fibrosis – which is absolutely critical because fibrosis pertains to a worse prognosis. [These results] are reasonably likely to predict clinical benefit in a phase 3 trial in patients with NASH,” he added.
 

FDA-chosen endpoints likely to predict clinical outcomes

The ongoing 54-month, phase 3, registrational, double-blind, placebo-controlled trial involved taking liver biopsies from 966 patients at around 200 global sites. Biopsy readings were taken by two pathologists that were then combined into a single treatment effect. 

Patients had biopsy-proven NASH with fibrosis stages F1B, F2, or F3, the presence of three or more metabolic risk factors, a FibroScan vibration-controlled transient elastography (VCTE) score of 8.5 kPa or more, baseline MRI proton density fat fraction (MRI-PDFF) of 8% or more, and a NAS score of 4 or more with at least 1 in each NAS component. Around 65% of participants had type 2 diabetes, between 13% and 16% were taking glucagonlike peptide-1 (GLP-1) receptor agonists, and 46%-51% were taking statins.

Patients were randomized 1:1:1 to once-daily resmetirom 80 mg or 100 mg orally or to placebo and treated for 52 weeks.

Both liver histological improvement primary endpoints at week-52 were proposed by the U.S. Food and Drug Administration as reasonably likely to predict clinical benefit and as such support accelerated approval for the treatment of NASH with liver fibrosis. These primary endpoints were NASH resolution (ballooning 0, inflammation 0/1) with ≥ 2-point improvement in NAS with no worsening of fibrosis, and ≥ 1-stage reduction in fibrosis with no worsening of NAS.

Patients on resmetirom showed improvement in NAS components and fibrosis, and less worsening of NAS and fibrosis, compared with placebo. Percentage improvement was seen in 31%, 33%, and 15% of patients on 80 mg resmetirom, 100 mg resmetirom, and placebo respectively; no change was seen in 51%, 48%, and 51% respectively; and worsening was seen in 18%, 19%, and 34% respectively. 

The key secondary endpoint of LDL cholesterol lowering was also met. “There was a significant effect of resmetirom 80 and 100 mg on multiple atherogenic lipids/lipoproteins at both week 24 and 52,” reported Dr. Harrison. The 52-week percentage change from baseline in LDL cholesterol was –14%, –20%, and 0% for the 80-mg resmetirom group, the 100-mg group, and the placebo group respectively.

“We also saw a significant reduction in liver enzymes [alanine transaminase, aspartate transaminase, and gamma-glutamyl transferase (GGT)] relative to placebo both in terms of percentage and absolute measures,” Dr. Harrison added. “[And] the change in liver enzymes was associated with the neutral biomarker that increases with resmetirom target engagement.”   

Resmetirom at both doses also resulted in a significant effect on MRI-PDFF and Fibroscan CAP. At week 52, 80 mg resmetirom, 100 mg, and placebo led to –42.1%, –51.4% and –10.4% change from baseline in MRI-PDFF, while Fibroscan CAP changed by –39.6%, –41.3%, and –14.5% respectively, reported Dr. Harrison. Liver volume dropped by –21.6% in the 80-mg group and –25.8% in the 100-mg group, compared with –1.0% in the placebo group. Spleen volume changed by –5.9%, –6.1%, and +3.2% respectively.

Liver stiffness, as measured by Fibroscan VCTE at week 52, changed from –3.7 KPa (F1B) to –2.0 KPa (F3) at 80 mg, and from –3.7 KPa (F1B) to –2.5 KPa (F2) and –3.3 KPa (F3) at the 100-mg dose.

Further analysis showed that improvements in fibrosis and NASH resolution were seen across all key subgroups, including baseline fibrosis stage (F2 or F3), NAS (< 6, ≥ 6), type 2 diabetes status, age (< 65 years, ≥ 65 years), and sex.
 

Safety profile

“The safety profile of resmetirom in the MAESTRO-NASH trial is consistent with previous phase 2/3 trials in which the most common adverse events were diarrhea and nausea at treatment initiation,” said Dr. Harrison.

Study discontinuations in the 100-mg group were increased relative to placebo during the first few weeks of treatment and were similar in all treatment groups up to 52 weeks. Discontinuations of patients on resmetirom 100 mg were mainly gastrointestinal related. 

Phase 2 results of the serial liver biopsy trial in adults with biopsy-confirmed NASH showed that resmetirom resolved NASH in a significantly greater percentage of patients and reduced liver enzymes, inflammatory biomarkers, and fibrosis, compared with placebo.

“We’ve been waiting for a long, long time for a therapy for these patients because until now, they have been challenged with lifestyle modifications to lose and maintain weight,” said Dr. Harrison. “There’s been a delay in identifying patients with this disease because we’ve had no treatment, but now that we are on the forefront of a treatment, it allows clinicians to open their minds to the possibility of identifying these patients.”

Dr. Harrison noted that a limitation of these data was the lack of clinical outcomes data to correlate with the biopsy data; however, the MAESTRO-NASH trial will continue to 54 months to accrue and evaluate clinical outcomes.

Milan Mishkovikj, MSc, board director of the European Liver Patients Association, Bitola, North Macedonia, commented on the potential benefit of this drug for patients. “Adhering to a healthy lifestyle is not always easy – not in all countries – so it’s encouraging to have a drug that hopefully is affordable and accessible to us. Now we need to manage the expectations of patients and caregivers.”

EASL’s vice secretary Aleksander Krag, MD, PhD, professor and head of hepatology at University of Southern Denmark, Odense, and Odense University Hospital remarked, “This is so exciting. This phase 3 trial is a real game-changer in the field of fatty liver disease because it has nearly 1,000 patients over 52 weeks of treatment.”

Madrigal Pharmaceuticals plans to submit an application to the FDA by end of the second quarter with a priority review.

Dr. Harrison is founder of Madrigal Pharmaceuticals. Dr. Krag has served as speaker for Norgine, Siemens, and Nordic Bioscience, and participated in advisory boards for Norgine and Siemens, all outside the submitted work. He receives royalties from Gyldendal and Echosens. Dr. Mishkovikj has declared no relevant financial relationships.

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

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

A Massachusetts-based law firm has filed a class action lawsuit against Harvard Medical School, alleging that it failed to protect the remains of people who donated their bodies to the university for research and education.

Plaintiffs include relatives of people whose remains were allegedly stolen and sold. The lawsuit alleges that as many as 400 cadavers may have been trafficked in a multi-year scheme. Details were revealed in a June 13 indictment by the U.S. attorney for the Middle District of Pennsylvania.

“Medical schools like Harvard have a duty to ensure [donated remains] are handled properly and with decency and to ensure they are used for their intended purpose of scientific study,” attorney Jeff Catalano said in a statement.

“I do think Harvard has that duty,” said Arthur Caplan, PhD, director, Division of Medical Ethics, New York University. But, he added, “I will say there’s not much they can do when employees set out to systematically undermine them.”

The indictment alleges that from 2018 through August 2022, Harvard morgue manager Cedric Lodge stole dissected portions of donated cadavers, including heads, brains, skin, and bones, which were then sold by him and his wife, Denise Lodge, to Katrina Maclean, owner of Kat’s Creepy Creations, Peabody, Mass. Ms. Maclean allegedly sold human remains to Joshua Taylor and Jeremy Pauley, both Pennsylvania residents.

On occasion, Mr. Lodge allowed Ms. Maclean, Mr. Taylor, and others into the morgue to choose which parts they wanted, according to the indictment. Mr. Taylor, Ms. Maclean, and Denise Lodge are all named in the indictment. Mr. Pauley was charged separately.

They each face a maximum of 15 years in prison.

Ms. Maclean allegedly bought two dissected faces for $600 and shipped human skin to Mr. Pauley to be made into leather; Mr. Pauley then eventually shipped the “tanned human skin” back to Ms. Maclean, according to the indictment. Over a 3-year period, Mr. Taylor paid the Lodges some $37,000 for stolen human remains, the indictment charges.

Mr. Pauley also purchased human remains from Candace Chapman Scott, who stole them from her employer, a mortuary in Little Rock, Ark. The mortuary received remains for cremation from an area medical school, according to the indictment.

After being notified of the investigation in March, Harvard cooperated fully, the school said in a statement from George Q. Daley, MD, PhD, dean of the Faculty of Medicine.

“We are appalled to learn that something so disturbing could happen on our campus – a community dedicated to healing and serving others,” the statement said. “The reported incidents are a betrayal of HMS and, most importantly, each of the individuals who altruistically chose to will their bodies to HMS through the Anatomical Gift Program to advance medical education and research.”

The U.S. attorney thanked Harvard for its cooperation, saying that it “is also a victim here.”

Dr. Caplan, who also writes an ethics column for this news organization, agrees. The school was betrayed, he said.

“You expect professionalism, integrity on the part of your doctors, on the part of your technicians, on the part of your workforce,” he said. He noted that those expectations are explained in institutions’ codes of ethics and policies.

Harvard said Mr. Lodge had worked in the morgue since 1995 and that he took several leaves: from September 2021 to February 2022, and again starting February 14. The school terminated his employment on May 6.

His duties included intake of anatomic donors’ bodies. He coordinated embalming and oversaw the storage and movement of cadavers to and from teaching labs. When studies were complete, he prepared remains to be transported to and from the external crematorium and, when appropriate, for burial, according to a Harvard fact sheet for families.

The medical school has convened an outside expert panel to evaluate the Anatomical Gift Program and morgue policies and practices. The panel is expected to make its findings public at the end of the summer.

Dr. Caplan said he hoped the committee recommends unannounced audits of cadaver donation programs and medical tissue and bone suppliers, which could help expose illicit diversions. “You need to keep an eye, which no one seems to do because it’s a state issue and it’s not a priority, on that trade in body parts,” he said.

He believes other medical schools will reexamine their donation programs, especially given Harvard’s status.

“With a prominent place like that having this kind of problem, I can’t imagine there’s not a little bit of a scramble at a lot of the body programs to make sure that they know that things are as they should be,” Dr. Caplan said.

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

TOPLINE:

The less U.S. patients pay out of pocket for drugs that often have high copays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) agonists, the more adherent they are.

METHODOLOGY:

• Review of 90,041 U.S. adults who started a GLP-1 agonist (n = 39,149) or SGLT2 inhibitor (n = 50,892) in 2014-2020.
• Participants had type 2 diabetes, heart failure, or both.
• Data are from Clinformatics Data Mart, including both commercial and Medicare health insurance plans.
• Primary outcome: 12-month adherence to prescribed GLP-1 agonist or SGLT2 inhibitor.

TAKEAWAYS:

• U.S. adults with a lower drug copay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher copay.
• These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
• After full adjustment, patients with a high copay (≥ $50/month) were, after 12 months, 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a low copay (< $10/month) for these agents.

IN PRACTICE:

“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” say the authors.

STUDY DETAILS:

The study was led by Utibe R. Essien, MD, from the University of California, Los Angeles, and Balvindar Singh, MD, PhD, from the University of Pittsburgh, and included several authors from other U.S. centers.

LIMITATIONS:

Study could not exclude residual confounding.

Generalizability uncertain for those without health insurance or with public insurance.

Study did not have information on patient preferences associated with medication use, including specific reasons for poor adherence.

Possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities.

Study could not assess how copayments influenced initial prescription receipt or abandonment at the pharmacy, nor other factors including possible price inflation.
 

DISCLOSURES:

The study received no commercial funding. One author (not a lead author) is an advisor to several drug companies, including ones that market SGLT2 inhibitors or GLP-1 agonists.

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

TOPLINE:

The less U.S. patients pay out of pocket for drugs that often have high copays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) agonists, the more adherent they are.

METHODOLOGY:

• Review of 90,041 U.S. adults who started a GLP-1 agonist (n = 39,149) or SGLT2 inhibitor (n = 50,892) in 2014-2020.
• Participants had type 2 diabetes, heart failure, or both.
• Data are from Clinformatics Data Mart, including both commercial and Medicare health insurance plans.
• Primary outcome: 12-month adherence to prescribed GLP-1 agonist or SGLT2 inhibitor.

TAKEAWAYS:

• U.S. adults with a lower drug copay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher copay.
• These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
• After full adjustment, patients with a high copay (≥ $50/month) were, after 12 months, 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a low copay (< $10/month) for these agents.

IN PRACTICE:

“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” say the authors.

STUDY DETAILS:

The study was led by Utibe R. Essien, MD, from the University of California, Los Angeles, and Balvindar Singh, MD, PhD, from the University of Pittsburgh, and included several authors from other U.S. centers.

LIMITATIONS:

Study could not exclude residual confounding.

Generalizability uncertain for those without health insurance or with public insurance.

Study did not have information on patient preferences associated with medication use, including specific reasons for poor adherence.

Possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities.

Study could not assess how copayments influenced initial prescription receipt or abandonment at the pharmacy, nor other factors including possible price inflation.
 

DISCLOSURES:

The study received no commercial funding. One author (not a lead author) is an advisor to several drug companies, including ones that market SGLT2 inhibitors or GLP-1 agonists.

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

TOPLINE:

The less U.S. patients pay out of pocket for drugs that often have high copays, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors or glucagon-like peptide-1 (GLP-1) agonists, the more adherent they are.

METHODOLOGY:

• Review of 90,041 U.S. adults who started a GLP-1 agonist (n = 39,149) or SGLT2 inhibitor (n = 50,892) in 2014-2020.
• Participants had type 2 diabetes, heart failure, or both.
• Data are from Clinformatics Data Mart, including both commercial and Medicare health insurance plans.
• Primary outcome: 12-month adherence to prescribed GLP-1 agonist or SGLT2 inhibitor.

TAKEAWAYS:

• U.S. adults with a lower drug copay had significantly higher odds of 12-month adherence to GLP-1 agonists and SGLT2 inhibitors, compared with those with a higher copay.
• These differences persisted after controlling for patient demographic, clinical, and socioeconomic covariates.
• After full adjustment, patients with a high copay (≥ $50/month) were, after 12 months, 53% less likely to adhere to an SGLT2 inhibitor and 32% less likely to adhere to a GLP-1 agonist, compared with patients with a low copay (< $10/month) for these agents.

IN PRACTICE:

“Lowering high out-of-pocket prescription costs may be key to improving adherence to guideline-recommended therapies and advancing overall quality of care in patients with type 2 diabetes and heart failure,” say the authors.

STUDY DETAILS:

The study was led by Utibe R. Essien, MD, from the University of California, Los Angeles, and Balvindar Singh, MD, PhD, from the University of Pittsburgh, and included several authors from other U.S. centers.

LIMITATIONS:

Study could not exclude residual confounding.

Generalizability uncertain for those without health insurance or with public insurance.

Study did not have information on patient preferences associated with medication use, including specific reasons for poor adherence.

Possible misclassifications of type 2 diabetes and heart failure diagnoses or medical comorbidities.

Study could not assess how copayments influenced initial prescription receipt or abandonment at the pharmacy, nor other factors including possible price inflation.
 

DISCLOSURES:

The study received no commercial funding. One author (not a lead author) is an advisor to several drug companies, including ones that market SGLT2 inhibitors or GLP-1 agonists.

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

Some patients continually cancel their appointments, ignore your medical directions, treat your staff rudely, or send you harassing emails.

Do you have to tolerate their behavior?

No, these are all appropriate reasons to terminate patients, attorneys say. Patients also can be dismissed for misleading doctors about their past medical history, chronic drug-seeking, displaying threatening or seductive behavior toward staff members or physicians, or any criminal behavior in the office, experts say.

But even if a reason seems legitimate, that doesn’t make it legal. Doctors should consider whether the reason is legal, said Chicago-area attorney Ericka Adler, JD, a partner at Roetzel & Andress, who advises doctors about terminating patients.

“Although a physician may think a reason to terminate a patient is legitimate, they should always be mindful of whether there is a legal concern at issue and consult with counsel if they’re unsure,” Ms. Adler said.

Terminating patients for an “illegal” reason such as discrimination based on race or gender or sexual orientation – even if couched as a legitimate patient issue – could open the practice to a lawsuit, Ms. Adler said.

Doctors also want to avoid patient abandonment claims by talking to the patient about problems and documenting them as they arise. If they can’t be resolved, doctors should ensure that there’s continuity of care when patients change physicians, said Ms. Adler.

About 90% of physicians have dismissed at least one patient during their career, according to a study of nearly 800 primary care practices. The most common reasons were legitimate: a patient was “extremely disruptive and/or behaved inappropriately toward clinicians or staff”; a patient had “violated chronic pain and controlled substance policies”; and a patient had “repeatedly missed appointments.” 

Jacqui O’Kane, DO, a family physician at South Georgia Medical Center in rural Nashville, said she has dismissed about 15 of 3,000 patients she has seen in the past 3 years at the clinic. Before she dismisses a patient, she looks at whether there has been a pattern of behavior and tries to talk to them about the problem first to find out if there are other reasons for it.

She also gives patients a warning: If the unacceptable behavior continues, it will lead to their dismissal.
 

When patients cross a line

Dr. O’Kane warned an elderly man who used the N-word with her that she wouldn’t tolerate that language in her office. Then, when he later called her front office employee the N-word, she decided to dismiss him.

“I said, ‘That’s it, you can’t say that to someone in this office. I already told you once, and you did it again. I’m sorry, you have to find another doctor,’ ” said Dr. O’Kane.

Another patient crossed a line when she missed four appointments, refused to come in, and kept sending Dr. O’Kane long messages on MyChart demanding medications and advice. One message was fairly obtrusive: “If you don’t give me something stronger for my nerves TODAY, I am going to LOSE MY MIND!!!” Dr. O’Kane said the patient wrote.

“I then told her that’s not how I run my practice and that she needed to find someone else.”

Another common reason doctors dismiss patients is for nonpayment, says Ms. Adler.

Recently, however, some patients have also begun demanding their money back from doctors for services already received and billed because they were unhappy about something that occurred at the doctor’s office, said Ms. Adler.

“I advise doctors to respond: ‘We disagree that you didn’t get the service, but we will give you your money back, and we’re also terminating you from our practice.’  At that point, the doctor-patient relationship has become impossible,” said Ms. Adler.
 

How to dismiss difficult patients ethically and legally

According to the AMA’s Council on Ethical and Judicial Affairs, a physician may not discontinue treatment of a patient if further treatment is medically indicated without giving the patient reasonable notice and sufficient opportunity to make alternative arrangements for care.

Terminating a patient abruptly without transferring their care could lead to a claim of patient abandonment and the physician being called before a licensing board for potentially violating the state’s Medical Practice Act, said Ms. Adler.

Doctors can take these six steps to set the stage for dismissal and avoid a claim of patient abandonment.

1. Create written policies. Medical practices can describe the rules and behavior they expect from patients in these policies, which can cover, for example, payment, treating staff with courtesy, and medications. “When the rules are in writing and patients sign off on them, that gives doctors a certain comfort level in being able to refer to them and say that the patient hasn’t been compliant,” said Ms. Adler.

She also recommends that your practice create a policy that doctors should let the patient know about their concerns and meet with them to discuss the problem before receiving a termination letter.

2. Document any consistent problems you’re having with a patient. When you start having problems with a patient, you should document when the problem occurred, how often it occurred, any discussions with the patient about the problem, warnings you gave the patient, and if and when you decided to terminate the patient.

3. Meet with the patient to discuss the problem. “Talking and meeting with a patient also allows the physician to assess whether there’s another issue. For example, is there a mental health concern? Is there a financial reason for nonpayment or no-shows? There are multiple benefits to finding out what the problem is,” said Ms. Adler.

Once you’ve decided to terminate a patient, here’s what you should do:

4. Allow enough time for the patient to find alternative care. Ms. Adler recommends giving patients 30 days’ notice and that physicians offer to provide emergency care during that time. However, if the patient is undergoing treatment or has other challenges, more time may be needed to transfer care.

“It’s important to consider the patient’s context – if the patient is receiving cancer treatment, or is in a late stage of pregnancy, or lives in a rural area where few specialists are available, you may want to treat them longer – at least until they finish their treatment,” said Ms. Adler. Also, states may have their own requirements about minimum notice periods, she said.

5. Provide patients with written notice that you intend to terminate their care. Ms. Adler recommends that each letter be tailored to the patient’s specific circumstances. “You could spell out a patient’s history of noncompliance or nonpayment or inappropriate conduct because it’s been documented and the patient is already aware of it from a previous discussion,” she said.

Ms. Adler also recommends that doctors consult with legal counsel when in doubt or if contacted by the patient’s lawyer. Some lawyers will draft the termination letters, she said.

6. Include the following information in the written letter: The date that they will no longer receive care, how they can obtain copies of their medical records, and how they can find a new physician by providing contact information for a state medical association or similar organization, which often maintains a database of clinicians by specialty and location.

The letter should also state that the doctor will provide emergency care during the 30 days. Ms. Adler also recommends sending the notice by certified mail.

Dr. O’Kane said she may be more likely to give patients a second chance because she practices in a rural underserved area, and she understands that her patients don’t have many other options for health care. She also has developed a reputation for being willing to take on difficult patients that other physicians didn’t want to deal with, she said.

She encourages physicians to talk to patients to find out why, for example, they may not be compliant with medications.

“The patient may say, ‘I had to choose between paying for medications and putting food on the table,’ ” said Dr. O’Kane.

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

Some patients continually cancel their appointments, ignore your medical directions, treat your staff rudely, or send you harassing emails.

Do you have to tolerate their behavior?

No, these are all appropriate reasons to terminate patients, attorneys say. Patients also can be dismissed for misleading doctors about their past medical history, chronic drug-seeking, displaying threatening or seductive behavior toward staff members or physicians, or any criminal behavior in the office, experts say.

But even if a reason seems legitimate, that doesn’t make it legal. Doctors should consider whether the reason is legal, said Chicago-area attorney Ericka Adler, JD, a partner at Roetzel & Andress, who advises doctors about terminating patients.

“Although a physician may think a reason to terminate a patient is legitimate, they should always be mindful of whether there is a legal concern at issue and consult with counsel if they’re unsure,” Ms. Adler said.

Terminating patients for an “illegal” reason such as discrimination based on race or gender or sexual orientation – even if couched as a legitimate patient issue – could open the practice to a lawsuit, Ms. Adler said.

Doctors also want to avoid patient abandonment claims by talking to the patient about problems and documenting them as they arise. If they can’t be resolved, doctors should ensure that there’s continuity of care when patients change physicians, said Ms. Adler.

About 90% of physicians have dismissed at least one patient during their career, according to a study of nearly 800 primary care practices. The most common reasons were legitimate: a patient was “extremely disruptive and/or behaved inappropriately toward clinicians or staff”; a patient had “violated chronic pain and controlled substance policies”; and a patient had “repeatedly missed appointments.” 

Jacqui O’Kane, DO, a family physician at South Georgia Medical Center in rural Nashville, said she has dismissed about 15 of 3,000 patients she has seen in the past 3 years at the clinic. Before she dismisses a patient, she looks at whether there has been a pattern of behavior and tries to talk to them about the problem first to find out if there are other reasons for it.

She also gives patients a warning: If the unacceptable behavior continues, it will lead to their dismissal.
 

When patients cross a line

Dr. O’Kane warned an elderly man who used the N-word with her that she wouldn’t tolerate that language in her office. Then, when he later called her front office employee the N-word, she decided to dismiss him.

“I said, ‘That’s it, you can’t say that to someone in this office. I already told you once, and you did it again. I’m sorry, you have to find another doctor,’ ” said Dr. O’Kane.

Another patient crossed a line when she missed four appointments, refused to come in, and kept sending Dr. O’Kane long messages on MyChart demanding medications and advice. One message was fairly obtrusive: “If you don’t give me something stronger for my nerves TODAY, I am going to LOSE MY MIND!!!” Dr. O’Kane said the patient wrote.

“I then told her that’s not how I run my practice and that she needed to find someone else.”

Another common reason doctors dismiss patients is for nonpayment, says Ms. Adler.

Recently, however, some patients have also begun demanding their money back from doctors for services already received and billed because they were unhappy about something that occurred at the doctor’s office, said Ms. Adler.

“I advise doctors to respond: ‘We disagree that you didn’t get the service, but we will give you your money back, and we’re also terminating you from our practice.’  At that point, the doctor-patient relationship has become impossible,” said Ms. Adler.
 

How to dismiss difficult patients ethically and legally

According to the AMA’s Council on Ethical and Judicial Affairs, a physician may not discontinue treatment of a patient if further treatment is medically indicated without giving the patient reasonable notice and sufficient opportunity to make alternative arrangements for care.

Terminating a patient abruptly without transferring their care could lead to a claim of patient abandonment and the physician being called before a licensing board for potentially violating the state’s Medical Practice Act, said Ms. Adler.

Doctors can take these six steps to set the stage for dismissal and avoid a claim of patient abandonment.

1. Create written policies. Medical practices can describe the rules and behavior they expect from patients in these policies, which can cover, for example, payment, treating staff with courtesy, and medications. “When the rules are in writing and patients sign off on them, that gives doctors a certain comfort level in being able to refer to them and say that the patient hasn’t been compliant,” said Ms. Adler.

She also recommends that your practice create a policy that doctors should let the patient know about their concerns and meet with them to discuss the problem before receiving a termination letter.

2. Document any consistent problems you’re having with a patient. When you start having problems with a patient, you should document when the problem occurred, how often it occurred, any discussions with the patient about the problem, warnings you gave the patient, and if and when you decided to terminate the patient.

3. Meet with the patient to discuss the problem. “Talking and meeting with a patient also allows the physician to assess whether there’s another issue. For example, is there a mental health concern? Is there a financial reason for nonpayment or no-shows? There are multiple benefits to finding out what the problem is,” said Ms. Adler.

Once you’ve decided to terminate a patient, here’s what you should do:

4. Allow enough time for the patient to find alternative care. Ms. Adler recommends giving patients 30 days’ notice and that physicians offer to provide emergency care during that time. However, if the patient is undergoing treatment or has other challenges, more time may be needed to transfer care.

“It’s important to consider the patient’s context – if the patient is receiving cancer treatment, or is in a late stage of pregnancy, or lives in a rural area where few specialists are available, you may want to treat them longer – at least until they finish their treatment,” said Ms. Adler. Also, states may have their own requirements about minimum notice periods, she said.

5. Provide patients with written notice that you intend to terminate their care. Ms. Adler recommends that each letter be tailored to the patient’s specific circumstances. “You could spell out a patient’s history of noncompliance or nonpayment or inappropriate conduct because it’s been documented and the patient is already aware of it from a previous discussion,” she said.

Ms. Adler also recommends that doctors consult with legal counsel when in doubt or if contacted by the patient’s lawyer. Some lawyers will draft the termination letters, she said.

6. Include the following information in the written letter: The date that they will no longer receive care, how they can obtain copies of their medical records, and how they can find a new physician by providing contact information for a state medical association or similar organization, which often maintains a database of clinicians by specialty and location.

The letter should also state that the doctor will provide emergency care during the 30 days. Ms. Adler also recommends sending the notice by certified mail.

Dr. O’Kane said she may be more likely to give patients a second chance because she practices in a rural underserved area, and she understands that her patients don’t have many other options for health care. She also has developed a reputation for being willing to take on difficult patients that other physicians didn’t want to deal with, she said.

She encourages physicians to talk to patients to find out why, for example, they may not be compliant with medications.

“The patient may say, ‘I had to choose between paying for medications and putting food on the table,’ ” said Dr. O’Kane.

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

Some patients continually cancel their appointments, ignore your medical directions, treat your staff rudely, or send you harassing emails.

Do you have to tolerate their behavior?

No, these are all appropriate reasons to terminate patients, attorneys say. Patients also can be dismissed for misleading doctors about their past medical history, chronic drug-seeking, displaying threatening or seductive behavior toward staff members or physicians, or any criminal behavior in the office, experts say.

But even if a reason seems legitimate, that doesn’t make it legal. Doctors should consider whether the reason is legal, said Chicago-area attorney Ericka Adler, JD, a partner at Roetzel & Andress, who advises doctors about terminating patients.

“Although a physician may think a reason to terminate a patient is legitimate, they should always be mindful of whether there is a legal concern at issue and consult with counsel if they’re unsure,” Ms. Adler said.

Terminating patients for an “illegal” reason such as discrimination based on race or gender or sexual orientation – even if couched as a legitimate patient issue – could open the practice to a lawsuit, Ms. Adler said.

Doctors also want to avoid patient abandonment claims by talking to the patient about problems and documenting them as they arise. If they can’t be resolved, doctors should ensure that there’s continuity of care when patients change physicians, said Ms. Adler.

About 90% of physicians have dismissed at least one patient during their career, according to a study of nearly 800 primary care practices. The most common reasons were legitimate: a patient was “extremely disruptive and/or behaved inappropriately toward clinicians or staff”; a patient had “violated chronic pain and controlled substance policies”; and a patient had “repeatedly missed appointments.” 

Jacqui O’Kane, DO, a family physician at South Georgia Medical Center in rural Nashville, said she has dismissed about 15 of 3,000 patients she has seen in the past 3 years at the clinic. Before she dismisses a patient, she looks at whether there has been a pattern of behavior and tries to talk to them about the problem first to find out if there are other reasons for it.

She also gives patients a warning: If the unacceptable behavior continues, it will lead to their dismissal.
 

When patients cross a line

Dr. O’Kane warned an elderly man who used the N-word with her that she wouldn’t tolerate that language in her office. Then, when he later called her front office employee the N-word, she decided to dismiss him.

“I said, ‘That’s it, you can’t say that to someone in this office. I already told you once, and you did it again. I’m sorry, you have to find another doctor,’ ” said Dr. O’Kane.

Another patient crossed a line when she missed four appointments, refused to come in, and kept sending Dr. O’Kane long messages on MyChart demanding medications and advice. One message was fairly obtrusive: “If you don’t give me something stronger for my nerves TODAY, I am going to LOSE MY MIND!!!” Dr. O’Kane said the patient wrote.

“I then told her that’s not how I run my practice and that she needed to find someone else.”

Another common reason doctors dismiss patients is for nonpayment, says Ms. Adler.

Recently, however, some patients have also begun demanding their money back from doctors for services already received and billed because they were unhappy about something that occurred at the doctor’s office, said Ms. Adler.

“I advise doctors to respond: ‘We disagree that you didn’t get the service, but we will give you your money back, and we’re also terminating you from our practice.’  At that point, the doctor-patient relationship has become impossible,” said Ms. Adler.
 

How to dismiss difficult patients ethically and legally

According to the AMA’s Council on Ethical and Judicial Affairs, a physician may not discontinue treatment of a patient if further treatment is medically indicated without giving the patient reasonable notice and sufficient opportunity to make alternative arrangements for care.

Terminating a patient abruptly without transferring their care could lead to a claim of patient abandonment and the physician being called before a licensing board for potentially violating the state’s Medical Practice Act, said Ms. Adler.

Doctors can take these six steps to set the stage for dismissal and avoid a claim of patient abandonment.

1. Create written policies. Medical practices can describe the rules and behavior they expect from patients in these policies, which can cover, for example, payment, treating staff with courtesy, and medications. “When the rules are in writing and patients sign off on them, that gives doctors a certain comfort level in being able to refer to them and say that the patient hasn’t been compliant,” said Ms. Adler.

She also recommends that your practice create a policy that doctors should let the patient know about their concerns and meet with them to discuss the problem before receiving a termination letter.

2. Document any consistent problems you’re having with a patient. When you start having problems with a patient, you should document when the problem occurred, how often it occurred, any discussions with the patient about the problem, warnings you gave the patient, and if and when you decided to terminate the patient.

3. Meet with the patient to discuss the problem. “Talking and meeting with a patient also allows the physician to assess whether there’s another issue. For example, is there a mental health concern? Is there a financial reason for nonpayment or no-shows? There are multiple benefits to finding out what the problem is,” said Ms. Adler.

Once you’ve decided to terminate a patient, here’s what you should do:

4. Allow enough time for the patient to find alternative care. Ms. Adler recommends giving patients 30 days’ notice and that physicians offer to provide emergency care during that time. However, if the patient is undergoing treatment or has other challenges, more time may be needed to transfer care.

“It’s important to consider the patient’s context – if the patient is receiving cancer treatment, or is in a late stage of pregnancy, or lives in a rural area where few specialists are available, you may want to treat them longer – at least until they finish their treatment,” said Ms. Adler. Also, states may have their own requirements about minimum notice periods, she said.

5. Provide patients with written notice that you intend to terminate their care. Ms. Adler recommends that each letter be tailored to the patient’s specific circumstances. “You could spell out a patient’s history of noncompliance or nonpayment or inappropriate conduct because it’s been documented and the patient is already aware of it from a previous discussion,” she said.

Ms. Adler also recommends that doctors consult with legal counsel when in doubt or if contacted by the patient’s lawyer. Some lawyers will draft the termination letters, she said.

6. Include the following information in the written letter: The date that they will no longer receive care, how they can obtain copies of their medical records, and how they can find a new physician by providing contact information for a state medical association or similar organization, which often maintains a database of clinicians by specialty and location.

The letter should also state that the doctor will provide emergency care during the 30 days. Ms. Adler also recommends sending the notice by certified mail.

Dr. O’Kane said she may be more likely to give patients a second chance because she practices in a rural underserved area, and she understands that her patients don’t have many other options for health care. She also has developed a reputation for being willing to take on difficult patients that other physicians didn’t want to deal with, she said.

She encourages physicians to talk to patients to find out why, for example, they may not be compliant with medications.

“The patient may say, ‘I had to choose between paying for medications and putting food on the table,’ ” said Dr. O’Kane.

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

Low-calorie tastes sweeter with a little salt

Diet and sugar-free foods and drinks seem like a good idea, but it’s hard to get past that strange aftertaste, right? It’s the calling card for the noncaloric aspartame- and stevia-containing sweeteners that we consume to make us feel like we can have the best of both worlds.

That weird lingering taste can be a total turn-off for some (raises hand), but researchers have found an almost facepalm solution to the not-so-sweet problem, and it’s salt.

Jason Tuinstra/Unsplash

Now, the concept of sweet and salty is not a far-fetched partnership when it comes to snack consumption (try M&Ms in your popcorn). The researchers at Almendra, a manufacturer of stevia sweeteners, put that iconic flavor pair to the test by adding mineral salts that have some nutritional value to lessen the effect of a stevia compound, rebaudioside A, found in noncaloric sweeteners.

The researchers added in magnesium chloride, calcium chloride, and potassium chloride separately to lessen rebaudioside A’s intensity, but they needed so much salt that it killed the sweet taste completely. A blend of the three mineral salts, however, reduced the lingering taste by 79% and improved the real sugar-like taste. The researchers tried this blend in reduced-calorie orange juice and a citrus-flavored soft drink, improving the taste in both.

The salty and sweet match comes in for the win once again. This time helping against the fight of obesity instead of making it worse.

Pseudomonas’ Achilles’ heel is more of an Achilles’ genetic switch

Today, on the long-awaited return of “Bacteria vs. the World,” we meet one of the rock stars of infectious disease.

LOTME: Through the use of imaginary technology, we’re talking to Pseudomonas aeruginosa. Thanks for joining us on such short notice, after Neisseria gonorrhoeae canceled at the last minute.

P. aeruginosa: No problem. I think we can all guess what that little devil is up to.

Benoit-Joseph Laventie, Biozentrum, University of Basel

LOTME: Bacterial resistance to antibiotics is a huge problem for our species. What makes you so hard to fight?

P. aeruginosa: We’ve been trying to keep that a secret, actually, but now that researchers in Switzerland and Denmark seem to have figured it out, I guess it’s okay for me to spill the beans.

LOTME: Beans? What do beans have to do with it?

P. aeruginosa: Nothing, it’s just a colloquial expression that means I’m sharing previously private information.

LOTME: Sure, we knew that. Please, continue your spilling.

P. aeruginosa: The secret is … Well, let’s just say we were a little worried when the Clash released “Should I Stay or Should I Go” back in the 1980s.

LOTME: The Clash? Now we’re really confused.

P. aeruginosa: The answer to their question, “Should I stay or should I go? is yes. Successful invasion of a human is all about division of labor. “While one fraction of the bacterial population adheres to the mucosal surface and forms a biofilm, the other subpopulation spreads to distant tissue sites,” is how the investigators described it. We can increase surface colonization by using a “job-sharing” process, they said, and even resist antibiotics because most of us remain in the protective biofilm.

LOTME: And they say you guys don’t have brains.

P. aeruginosa: But wait, there’s more. We don’t just divide the labor randomly. After the initial colonization we form two functionally distinct subpopulations. One has high levels of the bacterial signaling molecule c-di-GMP and stays put to work on the biofilm. The other group, with low levels of c-di-GMP, heads out to the surrounding tissue to continue the colonization. As project leader Urs Jenal put it, “By identifying the genetic switch, we have tracked down the Achilles heel of the pathogen.”

LOTME: Pretty clever stuff, for humans, anyway.

P. aeruginosa: We agree, but now that you know our secret, we can’t let you share it.

LOTME: Wait! The journal article’s already been published. Your secret is out. You can’t stop that by infecting me.

P. aeruginosa: True enough, but are you familiar with the fable of the scorpion and the frog? It’s our nature.

LOTME: Nooooo! N. gonorrhoeae wouldn’t have done this!
 

What a pain in the Butt

Businesses rise and businesses fall. We all know that one cursed location, that spot in town where we see businesses move in and close up in a matter of months. At the same time, though, there are also businesses that have been around as long as anyone can remember, pillars of the community.

Corydon, IN., likely has a few such long-lived shops, but it is officially down one 70-year-old family business as of late April, with the unfortunate passing of beloved local pharmacy Butt Drugs. Prescription pick-up in rear.

Bildflut/Wikimedia Commons

The business dates back to 1952, when it was founded as William H. Butt Drugs. We’re sure William Butt was never teased about his last name. Nope. No one would ever do that. After he passed the store to his children, it underwent a stint as Butt Rexall Drugs. When the shop was passed down to its third-generation and ultimately final owner, Katie Butt Beckort, she decided to simplify the name. Get right down to the bottom of things, as it were.

Butt Drugs was a popular spot, featuring an old-school soda fountain and themed souvenirs. According to Ms. Butt Beckort, people would come from miles away to buy “I love Butt Drugs” T-shirts, magnets, and so on. Yes, they knew perfectly well what they were sitting on.

So, if was such a hit, why did it close? Butt Drugs may have a hilarious name and merchandise to match, but the pharmacy portion of the pharmacy had been losing money for years. You know, the actual point of the business. As with so many things, we can blame it on the insurance companies. More than half the drugs that passed through Butt Drugs’ doors were sold at a loss, because the insurance companies refused to reimburse the store more than the wholesale price of the drug. Not even a good butt drug could clear up that financial diarrhea.

And so, we’ve lost Butt Drugs forever. Spicy food enthusiasts, coffee drinkers, and all patrons of Taco Bell, take a moment to reflect and mourn on what you’ve lost. No more Butt Drugs to relieve your suffering. A true kick in the butt indeed.

Low-calorie tastes sweeter with a little salt

Diet and sugar-free foods and drinks seem like a good idea, but it’s hard to get past that strange aftertaste, right? It’s the calling card for the noncaloric aspartame- and stevia-containing sweeteners that we consume to make us feel like we can have the best of both worlds.

That weird lingering taste can be a total turn-off for some (raises hand), but researchers have found an almost facepalm solution to the not-so-sweet problem, and it’s salt.

Jason Tuinstra/Unsplash

Now, the concept of sweet and salty is not a far-fetched partnership when it comes to snack consumption (try M&Ms in your popcorn). The researchers at Almendra, a manufacturer of stevia sweeteners, put that iconic flavor pair to the test by adding mineral salts that have some nutritional value to lessen the effect of a stevia compound, rebaudioside A, found in noncaloric sweeteners.

The researchers added in magnesium chloride, calcium chloride, and potassium chloride separately to lessen rebaudioside A’s intensity, but they needed so much salt that it killed the sweet taste completely. A blend of the three mineral salts, however, reduced the lingering taste by 79% and improved the real sugar-like taste. The researchers tried this blend in reduced-calorie orange juice and a citrus-flavored soft drink, improving the taste in both.

The salty and sweet match comes in for the win once again. This time helping against the fight of obesity instead of making it worse.

Pseudomonas’ Achilles’ heel is more of an Achilles’ genetic switch

Today, on the long-awaited return of “Bacteria vs. the World,” we meet one of the rock stars of infectious disease.

LOTME: Through the use of imaginary technology, we’re talking to Pseudomonas aeruginosa. Thanks for joining us on such short notice, after Neisseria gonorrhoeae canceled at the last minute.

P. aeruginosa: No problem. I think we can all guess what that little devil is up to.

Benoit-Joseph Laventie, Biozentrum, University of Basel

LOTME: Bacterial resistance to antibiotics is a huge problem for our species. What makes you so hard to fight?

P. aeruginosa: We’ve been trying to keep that a secret, actually, but now that researchers in Switzerland and Denmark seem to have figured it out, I guess it’s okay for me to spill the beans.

LOTME: Beans? What do beans have to do with it?

P. aeruginosa: Nothing, it’s just a colloquial expression that means I’m sharing previously private information.

LOTME: Sure, we knew that. Please, continue your spilling.

P. aeruginosa: The secret is … Well, let’s just say we were a little worried when the Clash released “Should I Stay or Should I Go” back in the 1980s.

LOTME: The Clash? Now we’re really confused.

P. aeruginosa: The answer to their question, “Should I stay or should I go? is yes. Successful invasion of a human is all about division of labor. “While one fraction of the bacterial population adheres to the mucosal surface and forms a biofilm, the other subpopulation spreads to distant tissue sites,” is how the investigators described it. We can increase surface colonization by using a “job-sharing” process, they said, and even resist antibiotics because most of us remain in the protective biofilm.

LOTME: And they say you guys don’t have brains.

P. aeruginosa: But wait, there’s more. We don’t just divide the labor randomly. After the initial colonization we form two functionally distinct subpopulations. One has high levels of the bacterial signaling molecule c-di-GMP and stays put to work on the biofilm. The other group, with low levels of c-di-GMP, heads out to the surrounding tissue to continue the colonization. As project leader Urs Jenal put it, “By identifying the genetic switch, we have tracked down the Achilles heel of the pathogen.”

LOTME: Pretty clever stuff, for humans, anyway.

P. aeruginosa: We agree, but now that you know our secret, we can’t let you share it.

LOTME: Wait! The journal article’s already been published. Your secret is out. You can’t stop that by infecting me.

P. aeruginosa: True enough, but are you familiar with the fable of the scorpion and the frog? It’s our nature.

LOTME: Nooooo! N. gonorrhoeae wouldn’t have done this!
 

What a pain in the Butt

Businesses rise and businesses fall. We all know that one cursed location, that spot in town where we see businesses move in and close up in a matter of months. At the same time, though, there are also businesses that have been around as long as anyone can remember, pillars of the community.

Corydon, IN., likely has a few such long-lived shops, but it is officially down one 70-year-old family business as of late April, with the unfortunate passing of beloved local pharmacy Butt Drugs. Prescription pick-up in rear.

Bildflut/Wikimedia Commons

The business dates back to 1952, when it was founded as William H. Butt Drugs. We’re sure William Butt was never teased about his last name. Nope. No one would ever do that. After he passed the store to his children, it underwent a stint as Butt Rexall Drugs. When the shop was passed down to its third-generation and ultimately final owner, Katie Butt Beckort, she decided to simplify the name. Get right down to the bottom of things, as it were.

Butt Drugs was a popular spot, featuring an old-school soda fountain and themed souvenirs. According to Ms. Butt Beckort, people would come from miles away to buy “I love Butt Drugs” T-shirts, magnets, and so on. Yes, they knew perfectly well what they were sitting on.

So, if was such a hit, why did it close? Butt Drugs may have a hilarious name and merchandise to match, but the pharmacy portion of the pharmacy had been losing money for years. You know, the actual point of the business. As with so many things, we can blame it on the insurance companies. More than half the drugs that passed through Butt Drugs’ doors were sold at a loss, because the insurance companies refused to reimburse the store more than the wholesale price of the drug. Not even a good butt drug could clear up that financial diarrhea.

And so, we’ve lost Butt Drugs forever. Spicy food enthusiasts, coffee drinkers, and all patrons of Taco Bell, take a moment to reflect and mourn on what you’ve lost. No more Butt Drugs to relieve your suffering. A true kick in the butt indeed.

Low-calorie tastes sweeter with a little salt

Diet and sugar-free foods and drinks seem like a good idea, but it’s hard to get past that strange aftertaste, right? It’s the calling card for the noncaloric aspartame- and stevia-containing sweeteners that we consume to make us feel like we can have the best of both worlds.

That weird lingering taste can be a total turn-off for some (raises hand), but researchers have found an almost facepalm solution to the not-so-sweet problem, and it’s salt.

Jason Tuinstra/Unsplash

Now, the concept of sweet and salty is not a far-fetched partnership when it comes to snack consumption (try M&Ms in your popcorn). The researchers at Almendra, a manufacturer of stevia sweeteners, put that iconic flavor pair to the test by adding mineral salts that have some nutritional value to lessen the effect of a stevia compound, rebaudioside A, found in noncaloric sweeteners.

The researchers added in magnesium chloride, calcium chloride, and potassium chloride separately to lessen rebaudioside A’s intensity, but they needed so much salt that it killed the sweet taste completely. A blend of the three mineral salts, however, reduced the lingering taste by 79% and improved the real sugar-like taste. The researchers tried this blend in reduced-calorie orange juice and a citrus-flavored soft drink, improving the taste in both.

The salty and sweet match comes in for the win once again. This time helping against the fight of obesity instead of making it worse.

Pseudomonas’ Achilles’ heel is more of an Achilles’ genetic switch

Today, on the long-awaited return of “Bacteria vs. the World,” we meet one of the rock stars of infectious disease.

LOTME: Through the use of imaginary technology, we’re talking to Pseudomonas aeruginosa. Thanks for joining us on such short notice, after Neisseria gonorrhoeae canceled at the last minute.

P. aeruginosa: No problem. I think we can all guess what that little devil is up to.

Benoit-Joseph Laventie, Biozentrum, University of Basel

LOTME: Bacterial resistance to antibiotics is a huge problem for our species. What makes you so hard to fight?

P. aeruginosa: We’ve been trying to keep that a secret, actually, but now that researchers in Switzerland and Denmark seem to have figured it out, I guess it’s okay for me to spill the beans.

LOTME: Beans? What do beans have to do with it?

P. aeruginosa: Nothing, it’s just a colloquial expression that means I’m sharing previously private information.

LOTME: Sure, we knew that. Please, continue your spilling.

P. aeruginosa: The secret is … Well, let’s just say we were a little worried when the Clash released “Should I Stay or Should I Go” back in the 1980s.

LOTME: The Clash? Now we’re really confused.

P. aeruginosa: The answer to their question, “Should I stay or should I go? is yes. Successful invasion of a human is all about division of labor. “While one fraction of the bacterial population adheres to the mucosal surface and forms a biofilm, the other subpopulation spreads to distant tissue sites,” is how the investigators described it. We can increase surface colonization by using a “job-sharing” process, they said, and even resist antibiotics because most of us remain in the protective biofilm.

LOTME: And they say you guys don’t have brains.

P. aeruginosa: But wait, there’s more. We don’t just divide the labor randomly. After the initial colonization we form two functionally distinct subpopulations. One has high levels of the bacterial signaling molecule c-di-GMP and stays put to work on the biofilm. The other group, with low levels of c-di-GMP, heads out to the surrounding tissue to continue the colonization. As project leader Urs Jenal put it, “By identifying the genetic switch, we have tracked down the Achilles heel of the pathogen.”

LOTME: Pretty clever stuff, for humans, anyway.

P. aeruginosa: We agree, but now that you know our secret, we can’t let you share it.

LOTME: Wait! The journal article’s already been published. Your secret is out. You can’t stop that by infecting me.

P. aeruginosa: True enough, but are you familiar with the fable of the scorpion and the frog? It’s our nature.

LOTME: Nooooo! N. gonorrhoeae wouldn’t have done this!
 

What a pain in the Butt

Businesses rise and businesses fall. We all know that one cursed location, that spot in town where we see businesses move in and close up in a matter of months. At the same time, though, there are also businesses that have been around as long as anyone can remember, pillars of the community.

Corydon, IN., likely has a few such long-lived shops, but it is officially down one 70-year-old family business as of late April, with the unfortunate passing of beloved local pharmacy Butt Drugs. Prescription pick-up in rear.

Bildflut/Wikimedia Commons

The business dates back to 1952, when it was founded as William H. Butt Drugs. We’re sure William Butt was never teased about his last name. Nope. No one would ever do that. After he passed the store to his children, it underwent a stint as Butt Rexall Drugs. When the shop was passed down to its third-generation and ultimately final owner, Katie Butt Beckort, she decided to simplify the name. Get right down to the bottom of things, as it were.

Butt Drugs was a popular spot, featuring an old-school soda fountain and themed souvenirs. According to Ms. Butt Beckort, people would come from miles away to buy “I love Butt Drugs” T-shirts, magnets, and so on. Yes, they knew perfectly well what they were sitting on.

So, if was such a hit, why did it close? Butt Drugs may have a hilarious name and merchandise to match, but the pharmacy portion of the pharmacy had been losing money for years. You know, the actual point of the business. As with so many things, we can blame it on the insurance companies. More than half the drugs that passed through Butt Drugs’ doors were sold at a loss, because the insurance companies refused to reimburse the store more than the wholesale price of the drug. Not even a good butt drug could clear up that financial diarrhea.

And so, we’ve lost Butt Drugs forever. Spicy food enthusiasts, coffee drinkers, and all patrons of Taco Bell, take a moment to reflect and mourn on what you’ve lost. No more Butt Drugs to relieve your suffering. A true kick in the butt indeed.

Prescriptions for desiccated thyroid extract (DTE) to treat newly diagnosed hypothyroidism nearly doubled between 2010 and 2020 in the United States, while prescribing of first-line levothyroxine monotherapy dropped, new research has found.

Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.

The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.

The magnitude of this shift in first-line treatment was unexpected.

“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.

Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.

“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.

Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
 

Why the increase in desiccated thyroid extract?

Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.

In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”

However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.

He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.

Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
 

Endocrinologists not as keen to prescribe DTE or T3

Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).

Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).

Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”

She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.

Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.

“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
 

Just trying to understand

Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.

Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”

“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.

Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”

Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.

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

Prescriptions for desiccated thyroid extract (DTE) to treat newly diagnosed hypothyroidism nearly doubled between 2010 and 2020 in the United States, while prescribing of first-line levothyroxine monotherapy dropped, new research has found.

Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.

The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.

The magnitude of this shift in first-line treatment was unexpected.

“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.

Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.

“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.

Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
 

Why the increase in desiccated thyroid extract?

Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.

In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”

However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.

He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.

Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
 

Endocrinologists not as keen to prescribe DTE or T3

Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).

Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).

Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”

She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.

Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.

“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
 

Just trying to understand

Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.

Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”

“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.

Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”

Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.

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

Prescriptions for desiccated thyroid extract (DTE) to treat newly diagnosed hypothyroidism nearly doubled between 2010 and 2020 in the United States, while prescribing of first-line levothyroxine monotherapy dropped, new research has found.

Nationwide MarketScan claims data reveal that, among first-time thyroid hormone prescriptions, those for DTE rose from 5.4% in 2010 to 10.2% in 2020. At the same time, prescriptions for first-line levothyroxine dropped from 91.8% to 87.2%. Prescriptions for liothyronine (LT3), primarily in combination with levothyroxine, remained at about 2% throughout the decade.

The nonlevothyroxine therapies were more commonly prescribed in the West and Southwestern United States, while levothyroxine monotherapy was more frequent in the Northwest and upper Midwest, and also in states with higher densities of primary care physicians and endocrinologists.

The magnitude of this shift in first-line treatment was unexpected.

“We were frankly quite surprised to see that difference in just 10 years,” lead author Matthew Ettleson, MD, of the University of Chicago, said in an interview.

Asked to comment, session moderator Elizabeth N. Pearce, MD, professor of medicine at Boston University Medical Center, said she also found the dramatic shift to DTE surprising.

“It’s unclear why since there hasn’t been a shift in the science or in the guidelines over the last decade. ... I think we need to understand better what is driving this, who the patients are who are seeking it out, and which providers are the primary drivers of these prescriptions,” she said.

Dr. Ettleson presented the findings at the annual meeting of the Endocrine Society. The results were simultaneously published in the Journal of Clinical Endocrinology and Metabolism.
 

Why the increase in desiccated thyroid extract?

Current guidelines by the American Thyroid Association recommend levothyroxine, a synthetic form of thyroxine (T4) monotherapy, as the standard of care for treating hypothyroidism. However, approximately 10%-20% of levothyroxine-treated patients report bothersome symptoms despite normalization of thyroid-stimulating hormone (TSH) levels.

In 2021, the ATA, along with European and British thyroid societies, issued a consensus statement noting that new trials of triiodothyronine (T3)/T4 combination therapy were “justified.”

However, the MarketScan data were gathered before that statement came out, which doesn’t mention desiccated thyroid extract, “so that’s a bit of a head-scratcher,” Ettleson said.

He said one possibility may be the existence of online materials saying negative things about levothyroxine, so that “people who are just learning about hypothyroidism might already be primed to think about alternative treatments.” Moreover, some patients may view DTE as more “natural” than levothyroxine.

Dr. Ettleson also noted that the distinct geographic variation “didn’t seem random. ... So not only was there a doubling overall but there’s a variation in practice patterns across the country. I don’t have an explanation for that, but I think it’s important to recognize in the medical community that there are these big differences.”
 

Endocrinologists not as keen to prescribe DTE or T3

Residence in a state with higher endocrinologist density (3.0/100,000 population) was associated with a decreased likelihood of receiving T3 (adjusted odds ratio, 0.33; P < .001) or DTE therapy (aOR, 0.18; P < .001).

Residence in large central metro zones was associated with an increased likelihood of receiving T3 (aOR, 1.32; P < .001) or DTE therapy (aOR, 1.05; P < .008, respectively).

Dr. Pearce observed: “I don’t see DTE in Boston. It’s mostly in the South and Southwest.”

She said she doubted that endocrinologists were the primary prescribers of DTE, as many endocrinologists are “wary” of the pig thyroid–derived product because its T4 to T3 ratio is about 4:1, in contrast to the ratio in humans of 13-14:1.

Thus, DTE contains a much higher proportion of the active hormone T3. It is also much shorter acting, with a half-life of a few hours, compared to a few days for T4, she explained.

“We don’t really know what long-term safety effects are but it’s probably a less physiologic way of dosing thyroid hormone than ... either levothyroxine or levothyroxine in combination with a lower T3 proportion,” she said.
 

Just trying to understand

Dr. Ettleson emphasized that the goal of his research wasn’t to reverse the trend but to better understand it.

Nonetheless, he also noted, “now that we know there are more patients taking DTE, we need to start looking at rates of atrial fibrillation, fracture, heart failure, and other possible outcomes in this population and compare them with levothyroxine and nonthyroid populations to make sure that it is as safe as levothyroxine.”

“There are no data to suggest increased risk, especially if TSH is monitored and stays in the normal range, but there’s very little data for over 5 or 10 years on DTE-treated patients. We need the data,” he emphasized.

Meanwhile, he’s working on a survey of endocrinologists and non-endocrinologists to ask if they’ve prescribed DTE, and if so, why, and whether it’s because patients asked for it. “There’s a lot more work to be done, but I think it’s exciting. It’s important to see how patients are being treated in the real world ... and understand why it’s happening and what the outcomes are.”

Dr. Ettleson and Dr. Pearce have reported no relevant financial relationships.

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

1. Stride confidently into the room to greet your 84-year-old female patient.

2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”

3. Extend your clenched fist toward her chest and wait for her to reciprocate.

4. Smile awkwardly behind your mask while you wait.

5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.

6. Wait.

7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.

8. Wait a bit more.

9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.

10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.

It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.

There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.

Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.

webphotographeer/Getty

The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).

With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

1. Stride confidently into the room to greet your 84-year-old female patient.

2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”

3. Extend your clenched fist toward her chest and wait for her to reciprocate.

4. Smile awkwardly behind your mask while you wait.

5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.

6. Wait.

7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.

8. Wait a bit more.

9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.

10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.

It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.

There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.

Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.

webphotographeer/Getty

The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).

With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

1. Stride confidently into the room to greet your 84-year-old female patient.

2. Introduce yourself saying, “Hi, I’m Dr. Jeff Benabio.”

3. Extend your clenched fist toward her chest and wait for her to reciprocate.

4. Smile awkwardly behind your mask while you wait.

5. Advise that you are doing a fist bump instead of a handshake to prevent the spread of viruses.

6. Wait.

7. Explain that she can bump, also known as “dap,” you back by extending her clenched fist and bumping into yours.

8. Wait a bit more.

9. Lower your fist and pat her on the shoulder with your left hand. Do so gently so it doesn’t seem like you just did a quick right jab followed by a left hook.

10. Sit down diffidently and pray that you can help her so this office visit is not an utter disaster.

It seemed a good idea for 2020: Let’s stop shaking hands while we wait out this viral apocalypse. Sensible, but entering a patient room and just sitting down didn’t work. It felt cold, impolite – this isn’t the DMV. In medicine, a complete stranger has to trust us to get naked, tell intimate secrets, even be stuck by needles all within minutes of meeting. We needed a trust-building substitute greeting.

There was the Muslim hand-on-my-heart greeting. Or the Hindu “namaste” or Buddhist “amituofo” folded hands. Or perhaps the paternalistic shoulder pat? I went with the fist bump. With some of my partner docs, my old MBA squad, my neighbor, the fist bump felt natural, reciprocated without hesitation. But it fails with many patients. To understand why, it’s helpful to know the history of the fist bump, also known as the dap.

Dap is an acronym for Dignity And Pride. It’s a variation of a handshake that originated among Black soldiers in the Vietnam war as a means of showing fraternity and establishing connectedness. In Vietnam, 30% of the combat battalions were Black. Marginalized in the military and at home, they created a greeting that was meaningful and unique. The dap was a series of shakes, bumps, slaps, and hugs that was symbolic. It was a means of showing respect and humility, that no one is above others, that I’ve got your back and you’ve got mine. It was a powerful recognition of humanity and effective means of personal connection. It spread from the Black community to the general population and it exists still today. The choreographed pregame handshake you see so many NBA players engage in is a descendant of the dap. Like many rituals, it reinforces bonds with those who are your people, your team, those you trust.

webphotographeer/Getty

The more generalized version is the simple fist bump. It is widely used, notably by President Obama, and in the appropriate circumstance, will almost always be reciprocated. But it doesn’t work well to create trust with a stranger. With a patient for example, you are not showing them respect for some accomplishment. Nor are we connecting with them as a member of your team. Unless this is a patient whom you’ve seen many times before, a fist bump attempt might be met with “are you serious?” In fact, a survey done in 2016 asking infectious disease professionals what they thought of fist bumps as a greeting, very few replied it was a good idea. Most felt it was unprofessional. Not to mention that a fist bump does not symbolize an agreement in the way that a handshake does (and has done since at least the 9th century BC).

With COVID waning and masks doffed, I’ve found myself back to handshaking. Yes, I sanitize before and after, another ritual that has symbolic as well as practical significance. I get fewer sideways glances from my geriatric patients for sure. But I do still offer a little dap for my liquid nitrogen–survivor kids and for the occasional fellow Gen Xer. “Wonder Twin powers, activate!”

Dr. Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at dermnews@mdedge.com

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

After 100 years of insulin therapy, teplizumab, an immunotherapy for early-stage type 1 diabetes, has been approved for the first time in the United States and has been shown to delay the manifestation of clinical diabetes by 3 years on average. As a prerequisite for the use of the anti-CD3 antibody teplizumab, patients must undergo a general screening for type 1 diabetes. Whether this prerequisite makes sense was the subject of hot debate among experts at the Diabetes Congress in Berlin.

Anette-Gabriele Ziegler, MD, PhD, director of the Institute for Diabetes Research in Helmholtz Munich, argued that voluntary screening for type 1 diabetes should be included in standard care. “The first immunotherapy that delays type 1 diabetes has been approved in the U.S. for early stage 2. And this early stage can only be identified through prior screening, since no symptoms have manifested by this stage,” she said. This is the only way in which as many people as possible, particularly children, will benefit from the disease-delaying therapy, she added.
 

Two autoantibodies

One biomarker for the early diagnosis of type 1 diabetes is evidence of at least two positive islet cell antibodies. In one study of more than 13,000 children who were observed for 20 years, the specificity of these antibodies was 100%. “Every single child with a positive autoantibody test developed type 1 diabetes later on in their life,” Dr. Ziegler said. “Based on the results of this study, the early stages of type 1 diabetes were added to multiple guidelines.”

The early stage of type 1 diabetes is divided into the following three phases, depending on autoantibody detection and the level of glucose metabolism:

• Early stage 1: Two or more islet autoantibodies and normoglycemia.
• Early stage 2: Two or more islet autoantibodies and dysglycemia.
• Early stage 3: Symptoms, hyperglycemia, insulin therapy.

The aim of the ongoing FR1DA study is to ascertain whether the general population could also be screened for type 1 diabetes using this autoantibody. “Since 2015, children of kindergarten and school age have undergone screening, and to date, more than 170,000 have been tested,” said Dr. Ziegler. “At least two autoantibodies were detected in 0.3% of those screened.”
 

Education and care

The families of the children in whom early-stage type 1 diabetes was diagnosed were invited to take an oral glucose tolerance test (OGTT), to undergo measurement of hemoglobin A1c, and to take part in training and monitoring. “Education and competent, ongoing care are crucial for the efficacy of the screening,” Dr. Ziegler emphasized.

The OGTT revealed that 85% of the FR1DA children were still in early stage 1, another 11% were in early stage 2, and the remaining 4% were in early stage 3.

“Unfortunately, the 4% could no longer benefit from teplizumab, since the medication is not approved for manifest diabetes,” said Dr. Ziegler. “However, the 11% could receive teplizumab immediately, and then later on, the 85%, when they developed stage 2. Therefore, further observation of the children is also important.”

The speed at which the disease progresses from early stage 1 to early stage 2 can be stratified using IA2 antibodies, the 90-minute OGTT glucose value, and the HbA1c value. With regard to progression to clinical type 1 diabetes (stage 3), it was observed that the progression risk for the FR1DA children was similar to that of international birth cohorts with increased genetic risk. “Of course, there is still no 20-year follow-up like for BABYDIAB, DIPP, and DAISY, but as of yet, the progression rate is practically identical,” said Dr. Ziegler.
 

Dubious benefits?

The advantages of screening for type 1 diabetes would not be limited to potential access to preventive therapies and a smooth transition to insulin therapy at the correct point in time, according to Dr. Ziegler. Participation in the FR1DA study dramatically reduced the risk of diabetic ketoacidosis (DKA). Between 2015 and 2023, the overall rate of ketoacidosis associated with the manifestation of clinical type 1 diabetes was 4.3%. In contrast, the general DKA rate in Germany has remained largely unchanged for the last 2 decades at between 20% and 25%.

In addition, the FR1DA children exhibited better beta cell function and better metabolic function at clinical diagnosis of type 1 diabetes. This finding was observed in a comparison with children with a spontaneous diabetes diagnosis from the DiMelli study. “It is important that there is a lot of data that shows how, in the long term, this is associated with a better morbidity and mortality,” said Dr. Ziegler.

Despite the impressive data from the FR1DA study, not all diabetes experts are convinced that a general screening for type 1 diabetes would be beneficial. Beate Karges, MD, PhD, of the Clinic for Pediatric and Adolescent Medicine of the Bethlehem Hospital Stolberg (Germany) and the endocrinology and diabetology department at the University Hospital Aachen (Germany), stressed, “Screening makes sense if the disease is curable in the preclinical phase or if there is a significantly better prognosis in the event of early diagnosis and treatment.”
 

Severe side effects

Even with an early-stage diagnosis, curing type 1 diabetes is impossible. The new anti-CD3 antibody teplizumab merely delays the manifestation of symptoms for 3 years. However, this delay has its price. The summary of product characteristics for teplizumab contains warnings of severe lymphopenia lasting many weeks, cytokine release syndrome, severe infections, and hypersensitivity reactions. Furthermore, vaccinations may not be administered during teplizumab treatment and therefore must be completed in advance.

“Preventing type 1 diabetes is still not possible, we can only delay it, and the long-term efficacy and safety of this immunotherapy are not clear,” said Dr. Karges. She added that a significant reduction in the DKA rate – as observed in the FR1DA study – may be possible even without screening. This possibility was demonstrated by a model project in Stuttgart, Germany, in which the DKA rate was significantly reduced through education alone.
 

Education reduces ketoacidosis

“The families were given information about the early signs of type 1 diabetes during the education investigation. Through this [education], a reduction in the ketoacidosis rate from 28% to 16% was achieved,” said Dr. Karges. It is also known from studies of familial type 1 diabetes that secondary sufferers in the family only exhibit a DKA rate of 7%. “Through education within the family and awareness campaigns, the DKA rate can be reduced by 40%-65%,” said Dr. Karges.

Dr. Karges also doubts whether starting insulin therapy earlier “at the correct point in time” elicits long-term advantages. Secondary sufferers with familial type 1 diabetes have better HbA1c values in the first few years after diagnosis. “But as they progress beyond 2, towards 10 years, the difference in HbA1c values diminishes,” said Dr. Karges.

Whether the patient has DKA at type 1 diabetes diagnosis also seems to make little difference in the long term. “There is also no difference in the HbA1c value in the 2-10 years after diagnosis,” said Dr. Karges. “Glycemic control is not permanently improved in the event that treatment is started early,” she concluded.

“Type 1 diabetes can be delayed with an immune intervention, but to do so, we must also accept possible severe side effects in an otherwise healthy child,” she said. On the other hand, type 1 diabetes can be treated well. “With pumps and continuous glucose monitoring, insulin therapy in children and adolescents has become significantly safer and more effective,” she said.
 

New therapeutic options

Whether voluntary screening for type 1 diabetes eventually finds its way into standard care depends on the further development of preventive medications. Dr. Ziegler stressed that future preventive therapy does not need to be limited to the anti-CD3 antibody teplizumab.

For example, strategies such as high-dose oral insulin therapy are being investigated. Verapamil, which is used to treat hypertension, is also promising, since with it, beta cells were retained in early stage 3, and it improved their function. The fusion protein abatacept fell short of statistical significance in a recently published study. For Dr. Ziegler, one thing remains true. “The therapy of type 1 diabetes is about to undergo a renaissance.”

This article was translated from the Medscape German Edition. A version of this article appeared on Medscape.com.

The Food and Drug Administration has approved empagliflozin (Jardiance, Boehringer Ingelheim) and empagliflozin combined with metformin (Synjardy, BI) for the treatment of type 2 diabetes in children aged 10 years and older.

This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.

Olivier Le Moal/Getty Images

Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).

Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.

“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.

“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
 

Type 2 diabetes rising exponentially in children, mainly non-Whites

Type 2 diabetes is rising exponentially in children and adolescents in the United States.

Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and  it continues to rise.

A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.

Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.

At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.

Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.

Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).

“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.

“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.

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

The Food and Drug Administration has approved empagliflozin (Jardiance, Boehringer Ingelheim) and empagliflozin combined with metformin (Synjardy, BI) for the treatment of type 2 diabetes in children aged 10 years and older.

This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.

Olivier Le Moal/Getty Images

Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).

Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.

“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.

“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
 

Type 2 diabetes rising exponentially in children, mainly non-Whites

Type 2 diabetes is rising exponentially in children and adolescents in the United States.

Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and  it continues to rise.

A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.

Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.

At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.

Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.

Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).

“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.

“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.

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

The Food and Drug Administration has approved empagliflozin (Jardiance, Boehringer Ingelheim) and empagliflozin combined with metformin (Synjardy, BI) for the treatment of type 2 diabetes in children aged 10 years and older.

This approval represents only the second oral treatment option for children and adolescents with type 2 diabetes after metformin; the latter appears to be less effective for pediatric patients than for adults.

Olivier Le Moal/Getty Images

Injectable glucagonlike peptide–1 (GLP-1) agonists are also available for youth with type 2 diabetes. These include daily liraglutide (Victoza) and once-weekly extended-release exenatide (Bydureon/Bydureon BCise).

Jardiance has been approved for adults with type 2 diabetes since 2014, and Synjardy has been approved since 2015.

“Compared to adults, children with type 2 diabetes have limited treatment options, even though the disease and symptom onset generally progress more rapidly in children,” said Michelle Carey, MD, MPH.

“Today’s approvals provide much-needed additional treatment options for children with type 2 diabetes,” added Dr. Carey, associate director for therapeutic review for the division of diabetes, lipid disorders, and obesity in the FDA’s Center for Drug Evaluation and Research.
 

Type 2 diabetes rising exponentially in children, mainly non-Whites

Type 2 diabetes is rising exponentially in children and adolescents in the United States.

Data from the SEARCH for Diabetes in Youth study show that the incidence of type 2 diabetes among youth rose by about 5% per year between 2002 and 2015, and  it continues to rise.

A more recent study found that a doubling of cases occurred during the pandemic, with youth often presenting with more severe disease. The majority of cases are among non-White racial groups.

Safety and efficacy data for empagliflozin for children came from the Diabetes Study of Linagliptin and Empagliflozin in Children and Adolescents (DINAMO) trial. That trial included 157 patients aged 10-17 years with A1c of 7% or above. Patients were randomly assigned to receive empagliflozin 10 mg or 25 mg daily, linagliptin (a DPP-4 inhibitor) 5 mg, or placebo for 26 weeks. Over 90% were also taking metformin, 40% in combination with insulin. All patients were given diet and exercise advice.

At week 26, the children treated with empagliflozin showed an average 0.2 percentage point decrease in A1c, compared with a 0.7-point increase among those taking placebo. Use of empagliflozin was also associated with lower fasting plasma glucose levels compared with placebo.

Side effects were similar to those seen in adults except for a higher risk of hypoglycemia, regardless of other glucose-lowering therapies that were being taken.

Reduction in A1c for participants treated with linagliptin was not statistically significant in comparison with placebo. There was a numerical reduction of 0.34% (P = .2935).

“Across the lifespan, we know that people living with type 2 diabetes have a high risk for many diabetes complications, so it’s important to recognize and treat diabetes early in its course,” Lori Laffel, MD, lead investigator of the DINAMO study, said in a press release from BI.

“These findings are particularly important given the need for more therapeutic options, especially oral agents, to manage type 2 diabetes in young people as, to date, metformin [has been] the only globally available oral treatment for youth,” added Dr. Laffel, chief of the pediatric, adolescent, and young adult section at the Joslin Diabetes Center and professor of pediatrics at Harvard Medical School, Boston.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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

People with nonalcoholic fatty liver disease (NAFLD) are more likely to develop severe infections requiring hospitalization, according to findings from a large Swedish cohort study.

The increased risk was equal to one extra severe infection in every six patients with NAFLD by 20 years after diagnosis, wrote Fahim Ebrahimi, MD, of the Karolinska Institute in Stockholm, and coauthors.

“Accumulating evidence suggests that NAFLD can affect multiple organ systems, which is not surprising, as the liver has multiple functions – regulating metabolism and being a central organ of the immune system,” Dr. Ebrahimi said in an interview.

The study was published online in Clinical Gastroenterology and Hepatology.

“Up to a fifth of cells in the liver are immune cells that process numerous antigens and pathogens from the gastrointestinal tract,” Dr. Ebrahimi noted. “We were intrigued by experimental studies showing that, in NAFLD, many of these key immune cells become dysfunctional at various levels, which may affect disease progression, but at the same time also increase the susceptibility to viral, bacterial, and fungal infections.”

Patients with NAFLD have metabolic risk factors known to increase infection risk, but a smaller study by a different research group had found that NAFLD could independently predispose patients to bacterial infections.

To further explore a connection between NAFLD and infection risk, the researchers looked at data for 12,133 Swedish adults with simple steatosis, nonfibrotic steatohepatitis, noncirrhotic fibrosis, or cirrhosis caused by NAFLD confirmed by liver biopsies performed between 1969 and 2017.

Each patient was matched to five or more contemporary controls from the general population by age, sex, and region of residence. The authors conducted an additional analysis that also adjusted for education, country of birth, and baseline clinical comorbidities, including diabetes, obesity, dyslipidemia, and hypertension, as well as hospitalization preceding the biopsy and chronic obstructive pulmonary disease.

The primary endpoint was severe infections requiring hospital admission. Secondary endpoints included seven prespecified infection subgroups: sepsis; respiratory tract; most gastrointestinal infections; bacterial peritonitis; urogenital; muscle, skin, and soft tissue; and other infections.
 

Elevated risk at all NAFLD stages

Dr. Ebrahimi and colleagues found that over a median follow-up of 14 years, patients with NAFLD had a higher incidence of severe infections – most often respiratory or urinary tract infections – compared with those without NAFLD (32% vs. 17%, respectively).

Biopsy-confirmed NAFLD was also associated with a 71% higher hazard and a 20-year absolute excess risk of 17.3% for severe infections requiring hospital admission versus comparators. The elevated risk showed up in patients with steatosis and increased with the severity of NAFLD. Simple steatosis saw a 64% higher risk (adjusted hazard ratio, 1.64; 95% confidence interval, 1.55-1.73), whereas patients with cirrhosis saw a more than twofold higher risk, compared with controls (aHR, 2.32; 95% CI, 1.92-2.82).

When Dr. Ebrahimi and colleagues adjusted for parameters of the metabolic syndrome, they found an independent increased risk for severe infection. For patients with NAFLD, the increased risk may come from greater susceptibility to infections in general or to a more severe course of infections.

“Our study clearly demonstrates the complexity and high disease burden associated with NAFLD,” Dr. Ebrahimi said. “We are beginning to understand the different layers involved and will eventually move away from a liver-centric view to a more holistic view of the disease.”

Clinicians caring for patients with NAFLD need to be aware of the increased risk for infection, Dr. Ebrahimi said. They also should assess their patients’ vaccination status, and seek to control modifiable risk factors, such as diabetes.

Nancy Reau, MD, of Rush University, Chicago, described the study’s message as important.

“Patients with NAFLD and advancing liver disease are at risk for severe infections,” Dr. Reau said. “When we consider the fact that patients with advanced liver disease tend to die from infectious complications, awareness leading to early recognition and efficient treatment is imperative.”

The authors acknowledged the following limitations: only severe infections requiring hospitalization could be captured; whether infection led to decompensation or vice versa among patients with cirrhosis could not be determined; and detailed data on smoking, alcohol, vaccinations, body mass, and other potentially relevant measures were not available.

The Swiss National Science Foundation, Syskonen Svensson Foundation, and Bengt Ihre Foundation provided grants to Dr. Ebrahimi or coauthors. One coauthor disclosed previous research funding from Janssen and MSD. Dr. Reau disclosed receiving research support and consulting fees from AbbVie and Gilead, as well as consulting fees from Arbutus, Intercept, and Salix.

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