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SUSTAIN FORTE: Higher-dose semaglutide safely boosts glycemic control, weight loss
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
Accumulating evidence shows that
Just weeks after the Food and Drug Administration approved an increased, 2.4-mg/week dose of semaglutide (Wegovy) for the indication of weight loss, results from a new randomized study with 961 patients that directly compared the standard 1.0-mg weekly dose for glycemic control with a 2.0-mg weekly dose showed that, over 40 weeks, the higher dose produced modest incremental improvements in both A1c reduction and weight loss while maintaining safety.
“Once weekly 2.0-mg subcutaneous semaglutide [Ozempic] was superior to 1.0 mg in reducing A1c, with greater weight loss and a similar safety profile,” Juan P. Frias, MD, said at the annual scientific sessions of the American Diabetes Association while presenting results of the SUSTAIN FORTE trial.
Average impact of the increased efficacy was measured. In the study’s “treatment policy estimand” analysis (considered equivalent to an intention-to-treat analysis), the primary endpoint of the cut in average A1c fell by a further 0.18% among patients on the higher dose, compared with the lower-dose arm, a significant difference in patients who entered the study with an average A1c of 8.9%. The average incremental boost for weight loss on the higher dose was about 0.8 kg, a difference that just missed significance (P = .0535).
In the study’s “trial product estimand” analysis (which censors data when patients stop the study drug or add on rescue medications), the effects were slightly more robust. The 2-mg dose produced an average 0.23% incremental decrease in A1c, compared with 1 mg, and an average incremental 0.93-kg weight reduction, both significant, reported Dr. Frias, an endocrinologist and medical director of the National Research Institute in Los Angeles.
Dr. Frias highlighted that these modest average differences had a clinical impact for some patients. In the treatment product estimand analysis, the percentage of patients achieving an A1c level of less than 7.0% increased from 58% of those who received 1 mg semaglutide to 68% of those treated with 2 mg, and achievement of an A1c of less than 6.5% occurred in 39% of patients on 1 mg and in 52% of those on 2 mg.
A similar pattern existed for weight loss in the treatment product estimand. Weight loss of at least 5% happened in 51% of patients on the 1-mg dose and in 59% of those on the higher dose.
Gradual up-titration aids tolerance
“The GLP-1 receptor agonists have so many benefits, but we were concerned in the past about pushing the dose. We’ve learned more about how to do that so that patients can better tolerate it,” commented Robert A. Gabbay, MD, PhD, chief science and medicine officer of the ADA in Arlington, Va. “The challenge with the medications from this class has been tolerability.”
A key to minimizing adverse effects, especially gastrointestinal effects, from treatment with semaglutide and other GLP-1 receptor agonists has been more gradual up-titration to the target dose, Dr. Gabbay noted in an interview, and SUSTAIN FORTE took this approach. All patients started on a 0.25-mg injection of semaglutide once weekly for the first 4 weeks, followed by a 0.5-mg dose once weekly for 4 weeks, and then a 1.0 mg weekly dose. Patients in the arm randomized to receive 2.0 mg had one further dose escalation after receiving the 1.0-mg dose for 4 weeks.
The result was that gastrointestinal adverse effects occurred in 31% of patients maintained for 32 weeks on the 1-mg dose (with 40 total weeks of semaglutide treatment), and in 34% of patients who received the 2-mg dose for 28 weeks (and 40 total weeks of semaglutide treatment). Serious adverse events of all types occurred in 5% of patients in the 1-mg arm and in 4% of those on 2 mg. Total adverse events resulting in treatment discontinuation occurred in about 4.5% of patients in both arms, and discontinuations because of gastrointestinal effects occurred in about 3% of patients in both arms.
Severe hypoglycemia episodes occurred in 1 patient maintained on 1 mg weekly and in 2 patients in the 2-mg arm, while clinically significant episodes of hypoglycemia occurred in 18 patients on the 1-mg dose (4%) and in 12 of the patients on 2 mg (3%).
“It’s reassuring that the higher dose is tolerated,” commented Dr. Gabbay.
Several doses to choose from
SUSTAIN FORTE ran during 2019-2020 at about 125 centers in 10 countries, with roughly half the sites in the United States. It randomized adults with type 2 diabetes and an A1c of 8.0%-10.0% despite ongoing metformin treatment in all patients. Just over half the patients were also maintained on a sulfonylurea agent at entry. The enrolled patients had been diagnosed with diabetes for an average of about 10 years. They averaged 58 years of age, their body mass index averaged nearly 35 kg/m2, and about 58% were men.
The new evidence in support of a 2.0-mg weekly dose of semaglutide for patients with type 2 diabetes introduces a new wrinkle in a growing menu of dose options for this drug. On June 4, 2021, the FDA approved a weekly 2.4-mg dose of semaglutide for the indication of weight loss regardless of diabetes status in patients with a body mass index of 30 or higher (or in people at 27 or more with at least one weight-related comorbidity).
Dr. Gabbay suggested that, in practice, clinicians may focus more on treatment goals for individual patients rather than drug dose, especially with an agent that’s safer with slow dose titration.
In general, “clinicians establish a goal for each patient’s A1c; you use the drug dose that gets you there,” he observed.
SUSTAIN FORTE was sponsored by Novo Nordisk, the company that markets semaglutide. Dr. Frias has been a consultant to Novo Nordisk and numerous other companies, he has been a speaker on behalf of Lilly, Merck, and Sanofi, and he has received research funding from Novo Nordisk and numerous other companies. Dr. Gabbay had no relevant disclosures.
FROM ADA 2021
‘Stunning’ twincretin beats semaglutide for A1c, weight reduction in T2D
Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.
“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.
“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.
SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
Significant differences at each dose level
Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.
One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.
The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.
The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.
The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
An ‘impressive’ weight loss effect
Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .
“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
The important issue of dose
But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.
“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.
Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.
Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.
A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
Low rates of hypoglycemia
Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.
These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.
Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.
SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
Several more tirzepatide trials
Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.
The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.
The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.
Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.
“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.
“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.
SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
Significant differences at each dose level
Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.
One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.
The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.
The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.
The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
An ‘impressive’ weight loss effect
Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .
“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
The important issue of dose
But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.
“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.
Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.
Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.
A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
Low rates of hypoglycemia
Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.
These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.
Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.
SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
Several more tirzepatide trials
Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.
The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.
The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.
Tirzepatide, a novel “twincretin” agent, was superior to 1-mg semaglutide treatments for reducing both hemoglobin A1c levels and body weight in patients with type 2 diabetes in a pivotal, 40-week, head-to-head trial with nearly 1,900 randomized patients, one of four positive pivotal trial results reported for tirzepatide at the annual scientific sessions of the American Diabetes Association.
“Across all four studies we see a significant and clinically meaningful decrease in A1c, and robust weight loss. The results exceeded our expectations” for both these outcomes, said Laura Fernández Landó, MD, senior medical director for tirzepatide at Lilly, the company developing the agent, and a coauthor on the semaglutide comparison study as well as on other tirzepatide reports at the meeting.
“This opens up a new avenue for results in diabetes therapy,” Jens Juul Holst, MD, remarked in a press conference.
SURPASS-2 compared three different tirzepatide doses delivered once weekly by subcutaneous injection against a 1-mg weekly, subcutaneous dose of semaglutide (Ozempic) in 1,879 adults who had been diagnosed with type 2 diabetes for an average of almost 9 years. All patients were already on metformin treatment that had proved inadequate for controlling their hyperglycemia; enrolled patients had an average A1c of 8.28%. The trial’s primary endpoint was change from baseline in A1c levels after 40 weeks.
Significant differences at each dose level
Patients on each of the three tirzepatide doses – 5 mg, 10 mg, or 15 mg once weekly – showed dose-dependent reductions in A1c that, for each dose, were significantly better than the reduction achieved with semaglutide. The highest tirzepatide dose reduced A1c levels by an average of 0.45% more than what semaglutide achieved, reported first author Juan P. Frias, MD; Dr. Landó; and their coauthors.
One key secondary endpoint was weight reduction, and each of the three tirzepatide doses again produced significant incremental loss beyond what semaglutide produced. The 5-mg weekly dose of tirzepatide produced an average 1.9-kg additional weight loss, compared with semaglutide, while the 15-mg dose resulted in an average 5.5-kg loss beyond what semaglutide achieved and a total average weight loss of 11.2 kg from baseline.
The study’s additional key secondary endpoints, the percentages of patients reaching an A1c of less than 7%, and less than 5.7%, also showed significantly better numbers with tirzepatide. The highest tirzepatide dose pushed 86% of patients below the 7% mark, compared with 79% on semaglutide, and the top tirzepatide dose resulted in 46% of patients getting their A1c below 5.7%, compared with 19% of patients on semaglutide.
The findings are “stunning, I must stay, and those results included that up to half of the patients treated with high doses of tirzepatide may reach A1c levels of less than 5.7%, which is really, really unheard of,” said Dr. Holst, professor of endocrinology and metabolism at the University of Copenhagen. Along with the “weight losses at the same time of up to 12% in that patient group, we are seeing some completely unexpected and really shocking and wonderful new advances in the therapy,” added Dr. Holst.
The safety profile of tirzepatide was roughly similar to semaglutide’s and to that other agents in the glucagonlike peptide-1 receptor agonist (GLP-1 RA) class. Concurrently with the report at the meeting, the results also appeared in an article published online in the New England Journal of Medicine.
An ‘impressive’ weight loss effect
Weight loss on tirzepatide was “impressive,” commented Katherine R. Tuttle, MD, a nephrologist affiliated with the University of Washington and executive director for research at Providence Health Care in Spokane, Wash. Another striking feature of tirzepatide’s weight-loss effect was that it did not plateau during the 40 weeks of the study, Dr. Tuttle noted in an accompanying editorial that accompanied the published report, a finding that suggests the potential for additional weight loss from continued treatment .
“The weight loss is remarkable,” commented Rodolfo J. Galindo, MD, an endocrinologist at Emory University, Atlanta. While incremental reduction of A1c on the order of less than 0.5% is helpful, incremental weight loss of more than 10 lbs on tirzepatide, compared with semaglutide “will likely be a tie-breaker” for many clinicians and patients to favor tirzepatide over semaglutide or another GLP-1 RA agent, he said in an interview. Dr. Galindo also cited other important factors that he predicted will drive decisions on using tirzepatide or a GLP-1 RA once tirzepatide reaches the U.S. market: relative cost, access, and tolerability.
The important issue of dose
But the edge that tirzepatide showed over semaglutide for weight loss did not occur on a completely level playing field. The 1 mg/week dose of semaglutide used as the comparator in SURPASS-2 was the maximum dose available at the time the study began, but in June 2021 the Food and Drug Administration approved a 2.4 mg/week dose (Wegovy) labeled specifically for weight loss. Dr. Tuttle cited the limitation this introduces in her editorial.
“The dose issue is important,” she wrote. The doses of tirzepatide and semaglutide compared in SURPASS-2 “were not comparable in terms of weight outcomes” given that prior evidence showed that the 2.4 mg/week semaglutide dose is more appropriate for weight loss.
Dr. Tuttle also cited other factors to consider when assessing tirzepatide compared with agents in the GLP-1 RA class.
Several GLP-1 RA agents, including semaglutide, have proven efficacy for reducing rates of atherosclerotic cardiovascular events and albuminuria, and they also slow decline in kidney function and progression of diabetic kidney disease. No details on the renal effects of tirzepatide appeared in the SURPASS-2 report. A press release from Lilly in May 2021 briefly mentioned results from a meta-analysis of several clinical studies of tirzepatide that showed a nonsignificant effect from tirzepatide on the incidence of major cardiovascular adverse events (death from cardiovascular or undetermined causes, MI, stroke, and hospitalization for unstable angina) relative to comparator groups. Results from a dedicated cardiovascular outcomes trial in high-risk patients treated with tirzepatide, SURPASS-CVOT, are not expected until 2024.
A further limitation of SURPASS-2 was the demographics of the enrolled population, which had a low (0.4%) enrollment rate of Black patients, and a high proportion (70%) of Hispanic patients, Dr. Tuttle observed.
Low rates of hypoglycemia
Another notable finding from SURPASS-2 was the low incidence of clinically significant hypoglycemic events (blood glucose levels less than 54 mg/dL), which occurred in 0.2%-1.7% of patients on tirzepatide, depending on their dose, and in 0.4% of patients on semaglutide. Two patients in the tirzepatide cohort had severe hypoglycemia.
These numbers are reassuring, said Dr. Galindo, and reflect the safety of tirzepatide’s dual, incretin-like mechanisms of action that make it a “twincretin.” The molecule acts as both a GLP-1 RA, and as glucose-dependent insulinotropic polypeptide, an incretin that stimulates insulin release when blood sugar is high but also increases glucagon levels when blood sugar levels are normal or low. This dual action may help explain the apparent increased potency tirzepatide showed for both A1c reduction and weight loss, compared with semaglutide, which acts only as a GLP-1 RA.
Some experts have cited the uncertainty introduced by the open-label design of SURPASS-2, a decision necessitated by the distinctly different delivery devices used for tirzepatide and semaglutide, explained Dr. Landó. But she highlighted that double blinding applied to the three different tirzepatide dosages tested in the trial. Dr. Landó said that Lilly plans to seek FDA approval for all three tested tirzepatide doses to give clinicians and patients flexibility in applying the treatment.
SURPASS-2 used a prolonged dose-escalation protocol designed to minimize gastrointestinal adverse effects that started patients on a 2.5 mg weekly dose that then increased by 2.5 mg increments every 4 weeks until patients reached their assigned target dose. This meant that patients did not begin receiving the 15-mg/week dose until halfway through the trial.
Several more tirzepatide trials
Reports from two other pivotal trials for tirzepatide also appeared as posters at the meeting. SURPASS-5 compared tirzepatide with placebo in 475 patients inadequately controlled with titrated insulin glargine (Lantus). SURPASS-3 randomized 1,444 patients to tirzepatide or titrated insulin degludec (Tresiba). In both studies treatment with tirzepatide led to significantly better reductions in A1c and in weight loss than the comparator treatments. Results from a third pivotal trial, SURPASS-1 which compared tirzepatide against placebo in 478 treatment-naive patients, will come in a report scheduled for the second day of the meeting.
The results from all the recent tirzepatide trials show a consistent benefit across the continuum of patients with type 2 diabetes regardless of whether it’s recent onset or well-established disease, said Dr. Landó.
The SURPASS studies were sponsored by Lilly, the company developing tirzepatide, and the reports include several authors who are Lilly employees. Dr. Landó is a Lilly employee and stockholder. Dr. Tuttle has been a consultant to Lilly and to Novo Nordisk, the company that markets semaglutide, as well as to AstraZeneca, Bayer, Boehringer Ingelheim, Gilead, and Janssen. She has also received travel expenses from Kyokawa Hakko Kirin, and research funding from Bayer, Goldfinch Bio, and Lilly. Dr. Galindo has been a consultant to Lilly and to Novo Nordisk, as well as to Abbott Diabetes Care, Sanofi, Valeritas, and Weight Watchers, and his institution has received grant support on his behalf from Lilly, Novo Nordisk and Dexcom. Dr. Holst had no disclosures.
FROM ADA 2021
Unmanaged diabetes, high blood glucose tied to COVID-19 severity
Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.
Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.
In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.
Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.
“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
Links between diabetes and COVID-19
There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.
It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.
Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m2; 87% were Hispanic.
Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
Impact of unmanaged diabetes and high blood glucose
Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.
Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.
COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.
The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
Aggressive treatment needed
Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.
“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”
Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.
“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”
Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.
Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.
Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.
In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.
Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.
“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
Links between diabetes and COVID-19
There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.
It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.
Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m2; 87% were Hispanic.
Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
Impact of unmanaged diabetes and high blood glucose
Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.
Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.
COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.
The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
Aggressive treatment needed
Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.
“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”
Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.
“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”
Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.
Unmanaged diabetes and high blood glucose levels are linked to more severe COVID-19 and worse rates of recovery, according to results of a retrospective study.
Patients not managing their diabetes with medication had more severe COVID-19 and length of hospitalization, compared with those who were taking medication, investigator Sudip Bajpeyi, PhD, said at the annual scientific sessions of the American Diabetes Association.
In addition, patients with higher blood glucose levels had more severe COVID-19 and longer hospital stays.
Those findings underscore the need to assess, monitor, and control blood glucose, especially in vulnerable populations, said Dr. Bajpeyi, director of the Metabolic, Nutrition, and Exercise Research Laboratory in the University of Texas, El Paso, who added that nearly 90% of the study subjects were Hispanic.
“As public health decisions are made, we think fasting blood glucose should be considered in the treatment of hospitalized COVID-19 patients,” he said in a press conference.
Links between diabetes and COVID-19
There are now many reports in medical literature that link diabetes to increased risk of COVID-19 severity, according to Ali Mossayebi, a master’s student who worked on the study. However, there are fewer studies that have looked specifically at the implications of poor diabetes management or acute glycemic control, the investigators said.
It’s known that poorly controlled diabetes can have severe health consequences, including higher risks for life-threatening comorbidities, they added.
Their retrospective study focused on medical records from 364 patients with COVID-19 admitted to a medical center in El Paso. Their mean age was 60 years, and their mean body mass index was 30.3 kg/m2; 87% were Hispanic.
Acute glycemic control was assessed by fasting blood glucose at the time of hospitalization, while chronic glycemic control was assessed by hemoglobin A1c, the investigators said. Severity of COVID-19 was measured with the Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA), which is based on the patient’s respiratory rate, blood pressure, and mental status.
Impact of unmanaged diabetes and high blood glucose
Severity of COVID-19 severity and length of hospital stay were significantly greater in patients with unmanaged diabetes, as compared with those who reported that they managed their diabetes with medication, Dr. Bajpeyi and coinvestigators found.
Among patients with unmanaged diabetes, the mean qSOFA score was 0.22, as compared with 0.44 for patients with managed diabetes. The mean length of hospital stay was 10.8 days for patients with unmanaged diabetes and 8.2 days for those with medication-managed diabetes, according to the abstract.
COVID-19 severity and hospital stay length were highest among patients with acute glycemia, the investigators further reported in an electronic poster that was part of the ADA meeting proceedings.
The mean qSOFA score was about 0.6 for patients with blood glucose levels of at least 126 mg/dL and A1c below 6.5%, and roughly 0.2 for those with normal blood glucose and normal A1c. Similarly, duration of hospital stay was significantly higher for patients with high blood glucose and A1c as compared with those with normal blood glucose and A1c.
Aggressive treatment needed
Findings of this study are in line with previous research showing that in-hospital hyperglycemia is a common and important marker of poor clinical outcome and mortality, with or without diabetes, according to Rodolfo J. Galindo, MD, FACE, medical chair of the hospital diabetes task force at Emory Healthcare System, Atlanta.
“These patients need aggressive treatment of hyperglycemia, regardless of the diagnosis of diabetes or A1c value,” said Dr. Galindo, who was not involved in the study. “They also need outpatient follow-up after discharge, because they may develop diabetes soon after.”
Follow-up within is important because roughly 30% of patients with stress hyperglycemia (increases in blood glucose during an acute illness) will develop diabetes within a year, according to Dr. Galindo.
“We do not know in COVID-10 patients if it is only 30%,” he said, “Our thinking in our group is that it’s probably higher.”
Dr. Bajpeyi and coauthors reported no disclosures. Dr. Galindo reported disclosures related to Abbott Diabetes, Boehringer Ingelheim International, Eli Lilly, Novo Nordisk, Sanofi US, Valeritas, and Dexcom.
FROM ADA 2020
Pfizer halts distribution of stop-smoking pill Chantix
The pharmaceutical company is also recalling some lots of Chantix that may have high levels of NDMA, Reuters reported.
Pfizer told Reuters the distribution pause was ordered out of abundance of caution while further testing is conducted. The FDA approved varenicline, which is marketed as Chantix, in 2006.
“The benefits of Chantix outweigh the very low potential risks, if any, posed by nitrosamine exposure from varenicline on top of other common sources over a lifetime,” Pfizer spokesperson Steven Danehy said in an email, according to Reuters.
The FDA has not issued a recall on Chantix. In Canada, however, health authorities on June 8 instituted a recall for Champix, the name under which the drug is sold in that nation.
The Chantix website says it’s a 3- to 6-month treatment that helps people overcome the need to smoke tobacco. The website says more than 13 million people have been prescribed Chantix.
Other health concerns have been raised about Chantix, such as mental health side effects.
In 2016, however, researchers concluded Chantix did not appear to raise the risk of serious health disorders such as depression, anxiety, and suicidal thoughts.
A version of this article first appeared on WebMD.com.
The pharmaceutical company is also recalling some lots of Chantix that may have high levels of NDMA, Reuters reported.
Pfizer told Reuters the distribution pause was ordered out of abundance of caution while further testing is conducted. The FDA approved varenicline, which is marketed as Chantix, in 2006.
“The benefits of Chantix outweigh the very low potential risks, if any, posed by nitrosamine exposure from varenicline on top of other common sources over a lifetime,” Pfizer spokesperson Steven Danehy said in an email, according to Reuters.
The FDA has not issued a recall on Chantix. In Canada, however, health authorities on June 8 instituted a recall for Champix, the name under which the drug is sold in that nation.
The Chantix website says it’s a 3- to 6-month treatment that helps people overcome the need to smoke tobacco. The website says more than 13 million people have been prescribed Chantix.
Other health concerns have been raised about Chantix, such as mental health side effects.
In 2016, however, researchers concluded Chantix did not appear to raise the risk of serious health disorders such as depression, anxiety, and suicidal thoughts.
A version of this article first appeared on WebMD.com.
The pharmaceutical company is also recalling some lots of Chantix that may have high levels of NDMA, Reuters reported.
Pfizer told Reuters the distribution pause was ordered out of abundance of caution while further testing is conducted. The FDA approved varenicline, which is marketed as Chantix, in 2006.
“The benefits of Chantix outweigh the very low potential risks, if any, posed by nitrosamine exposure from varenicline on top of other common sources over a lifetime,” Pfizer spokesperson Steven Danehy said in an email, according to Reuters.
The FDA has not issued a recall on Chantix. In Canada, however, health authorities on June 8 instituted a recall for Champix, the name under which the drug is sold in that nation.
The Chantix website says it’s a 3- to 6-month treatment that helps people overcome the need to smoke tobacco. The website says more than 13 million people have been prescribed Chantix.
Other health concerns have been raised about Chantix, such as mental health side effects.
In 2016, however, researchers concluded Chantix did not appear to raise the risk of serious health disorders such as depression, anxiety, and suicidal thoughts.
A version of this article first appeared on WebMD.com.
MD jailed for road rage, career spirals downhill
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
It was a 95° F day in July 2015, and emergency physician Martin Maag, MD, was driving down Bee Ridge Road, a busy seven-lane thoroughfare in Sarasota, Fla., on his way home from a family dinner. To distance himself from a truck blowing black smoke, Dr. Maag says he had just passed some vehicles, when a motorcycle flew past him in the turning lane and the passenger flipped him off.
“I started laughing because I knew we were coming up to a red light,” said Dr. Maag. “When we pulled up to the light, I put my window down and said: ‘Hey, you ought to be a little more careful about who you’re flipping off! You never know who it might be and what they might do.’ ”
The female passenger cursed at Dr. Maag, and the two traded profanities. The male driver then told Dr. Maag: “Get out of the car, old man,” according to Dr. Maag. Fuming, Dr. Maag got out of his black Tesla, and the two men met in the middle of the street.
“As soon as I got close enough to see him, I could tell he really looked young,” Dr. Maag recalls. “I said: ‘You’re like 12 years old. I’m going to end up beating your ass and then I’m going to go to jail. Go get on your bike, and ride home to your mom.’ I don’t remember what he said to me, but I spun around and said: ‘If you want to act like a man, meet me up the street in a parking lot and let’s have at it like men.’ ”
The motorcyclist got back on his white Suzuki and sped off, and Dr. Maag followed. Both vehicles went racing down the road, swerving between cars, and reaching speeds of 100 miles per hour, Dr. Maag said. At one point, Dr. Maag says he drove in front of the motorcyclist to slow him down, and the motorcycle clipped the back of his car. No one was seriously hurt, but soon Dr. Maag was in the back of a police cruiser headed to jail.
Dr. Maag wishes he could take back his actions that summer day 6 years ago. Those few minutes of fury have had lasting effects on the doctor’s life. The incident resulted in criminal charges, a jail sentence, thousands of dollars in legal fees, and a 3-year departure from emergency medicine. Although Dr. Maag did not lose his medical license as a result of the incident, the physician’s Medicare billing privileges were suspended because of a federal provision that ties some felonies to enrollment revocations.
“Every doctor, every health professional needs to know that there are a lot of consequences that go with our actions outside of work,” he said. “In my situation, what happened had nothing to do with medicine, it had nothing to do with patients, it had nothing to do my professional demeanor. But yet it affected my entire career, and I lost the ability to practice emergency medicine for 3 years. Three years for any doctor is a long time. Three years for emergency medicine is a lifetime.”
The physician ends up in jail
After the collision, Dr. Maag pulled over in a parking lot and dialed 911. Several passing motorists did the same. It appeared the biker was trying to get away, and Dr. Maag was concerned about the damage to his Tesla, he said.
When police arrived, they heard very different accounts of what happened. The motorcyclist and his girlfriend claimed Dr. Maag was the aggressor during the altercation, and that he deliberately tried to hit them with his vehicle. Two witnesses at the scene said they had watched Dr. Maag pursue the motorcycle in his vehicle, and that they believed he crossed into their lane intentionally to strike the motorcycle, according to police reports.
“[The motorcyclist] stated that the vehicle struck his right foot when it hit the motorcycle and that he was able to keep his balance and not lay the bike down,” Sarasota County Deputy C. Moore wrote in his report. “The motorcycle was damaged on the right side near [his] foot, verifying his story. Both victims were adamant that the defendant actually and intentionally struck the motorcycle with his car due to the previous altercation.”
Dr. Maag told officers the motorcyclist had initiated the confrontation. He acknowledged racing after the biker, but said it was the motorcyclist who hit his vehicle. In an interview, Dr. Maag disputed the witnesses’ accounts, saying that one of the witnesses was without a car and made claims to police that were impossible from her distance.
In the end, the officer believed the motorcyclist, writing in his report that the damage to the Tesla was consistent with the biker’s version of events. Dr. Maag was handcuffed and taken to the Sarasota County Jail.
“I was in shock,” he said. “When we got to the jail, they got me booked in and fingerprinted. I sat down and said [to an officer]: ‘So, when do I get to bond out?’ The guy started laughing and said: ‘You’re not going anywhere. You’re spending the night in jail, my friend.’ He said: ‘Your charge is one step below murder.’”
‘I like to drive fast’
Aside from speeding tickets, Dr. Maag said he had never been in serious trouble with the law before.
The husband and father of two has practiced emergency medicine for more 15 years, and his license has remained in good standing. Florida Department of Health records show Dr. Maag’s medical license as clear and active with no discipline cases or public complaints on file.
“I did my best for every patient that came through that door,” he said. “There were a lot of people who didn’t like my personality. I’ve said many times: ‘I’m not here to be liked. I’m here to take care of people and provide the best care possible.’ ”
Sarasota County records show that Dr. Maag has received traffic citations in the past for careless driving, unlawful speed, and failure to stop at a red light, among others. He admits to having a “lead foot,” but says he had never before been involved in a road rage incident.
“I’m not going to lie, I like to drive fast,” he said. “I like that feeling. It just seems to slow everything down for me, the faster I’m going.”
After being booked into jail that July evening in 2015, Dr. Maag called his wife to explain what happened.
“She said, ‘I can’t believe you’ve done this. I’ve told you a million times, don’t worry about how other people drive. Keep your mouth shut,’” he recalled. “I asked her to call my work and let them know I wouldn’t be coming in the next day. Until that happened, I had never missed a day of work since becoming a physician.”
After an anxious night in his jail cell, Dr. Maag lined up with the other inmates the next morning for his bond hearing. His charges included felony, aggravated battery, and felony aggravated assault with a deadly weapon. A prosecutor recommended Dr. Maag’s bond be set at $1 million, which a judge lowered to $500,000.
Michael Fayard, a criminal defense attorney who represented Dr. Maag in the case, said even with the reduction, $500,000 was an outrageous bond for such a case.
“The prosecutor’s arguments to the judge were that he was a physician driving a Tesla,” Mr. Fayard said. “That was his exact argument for charging him a higher bond. It shouldn’t have been that high. I argued he was not a flight risk. He didn’t even have a passport.”
The Florida State Attorney’s Office did not return messages seeking comment about the case.
Dr. Maag spent 2 more nights in jail while he and his wife came up with $50,000 in cash, in accordance with the 10% bond rule. In the meantime, the government put a lien on their house. A circuit court judge later agreed the bond was excessive, according to Mr. Fayard, but by that time, the $50,000 was paid and Dr. Maag was released.
New evidence lowers charges
Dr. Maag ultimately accepted a plea deal from the prosecutor’s office and pled no contest to one count of felony criminal mischief and one count of misdemeanor reckless driving. In return, the state dropped the two more serious felonies. A no-contest plea is not considered an admission of guilt.
Mr. Fayard said his investigation into the road rage victim unearthed evidence that poked holes in the motorcyclist’s credibility, and that contributed to the plea offer.
“We found tons of evidence about the kid being a hot-rodding rider on his motorcycle, videos of him traveling 140 miles an hour, popping wheelies, and darting in and out of traffic,” he said. “There was a lot of mitigation that came up during the course of the investigation.”
The plea deal was a favorable result for Dr. Maag considering his original charges, Mr. Fayard said. He added that the criminal case could have ended much differently.
“Given the facts of this case and given the fact that there were no serious injuries, we supported the state’s decision to accept our mitigation and come out with the sentence that they did,” Mr. Fayard said. “If there would have been injuries, the outcome would have likely been much worse for Dr. Maag.”
With the plea agreement reached, Dr. Maag faced his next consequence – jail time. He was sentenced to 60 days in jail, a $1,000 fine, 12 months of probation, and 8 months of house arrest. Unlike his first jail stay, Dr. Maag said the second, longer stint behind bars was more relaxing.
“It was the first time since I had become an emergency physician that I remember my dreams,” he recalled. “I had nothing to worry about, nothing to do. All I had to do was get up and eat. Every now and then, I would mop the floors because I’m kind of a clean freak, and I would talk to guys and that was it. It wasn’t bad at all.”
Dr. Maag told no one that he was a doctor because he didn’t want to be treated differently. The anonymity led to interesting tidbits from other inmates about the best pill mills in the area for example, how to make crack cocaine, and selling items for drugs. On his last day in jail, the other inmates learned from his discharge paperwork that Dr. Maag was a physician.
“One of the corrections officers said: ‘You’re a doctor? We’ve never had a doctor in here before!’” Dr. Maag remembers. “He said: ‘What did a doctor do to get into jail?’ I said: ‘Do you really want to know?’ ”
About the time that Dr. Maag was released from jail, the Florida Board of Medicine learned of his charges and began reviewing his case. Mr. Fayard presented the same facts to the board and argued for Dr. Maag to keep his license, emphasizing the offenses in which he was convicted were significantly less severe than the original felonies charged. The board agreed to dismiss the case.
“The probable cause panel for the board of medicine considered the complaint that has been filed against your client in the above referenced case,” Peter Delia, then-assistant general counsel for the Florida Department of Health, wrote in a letter dated April 27, 2016. “After careful review of all information and evidence obtained in this case, the panel determined that probable cause of a violation does not exist and directed this case to be closed.”
A short-lived celebration
Once home, Dr. Maag was on house arrest, but he was granted permission to travel for work. He continued to practice emergency medicine. After several months, authorities dropped the house arrest, and a judge canceled his probation early. It appeared the road rage incident was finally behind him.
But a year later, in 2018, the doctor received a letter from the Centers for Medicare & Medicaid Services informing him that because of his charges, his Medicare number had been revoked in November 2015.
“It took them 3 years to find me and tell me, even though I never moved,” he said. “Medicare said because I never reported this, they were hitting me up with falsification of documentation because I had signed other Medicare paperwork saying I had never been barred from Medicare, because I didn’t know that I was.”
Dr. Maag hired a different attorney to help him fight the 3-year enrollment ban. He requested reconsideration from CMS, but a hearing officer in October 2017 upheld the revocation. Because his privileges had been revoked in 2015, Dr. Maag’s practice group had to return all money billed by Dr. Maag to Medicare over the 3-year period, which totaled about $190,000.
A CMS spokeswoman declined to comment about Dr. Maag’s case, referring a reporter for this news organization to an administrative law judge’s decision that summarizes the agency’s findings.
According to the summary, in separate reconsidered determinations, the CMS hearing officer concluded that the revocation was proper under section 424.535(a)(3). The regulation, enacted in 2011, allows CMS to revoke billing privileges if a provider was convicted of a federal or state felony within the preceding 10 years that the agency determines is detrimental to the Medicare program and its beneficiaries.
The hearing officer reasoned that Dr. Maag “had been convicted of a felony that is akin to assault and, even if it were not, his actions showed a reckless disregard for the safety of others.” She concluded also that CMS could appropriately revoke Dr. Maag’s Medicare enrollment because he did not report his felony conviction within 30 days as required.
Dr. Maag went through several phases of fighting the revocation, including an appeal to the Department of Health & Human Services Departmental Appeals Board. He argued that his plea was a no-contest plea, which is not considered an admission of guilt. Dr. Maag and his attorney provided CMS a 15-page paper about his background, education, career accomplishments, and patient care history. They emphasized that Dr. Maag had never harmed or threatened a patient, and that his offense had nothing to do with his practice.
In February 2021, Judge Carolyn Cozad Hughes, an administrative law judge with CMS, upheld the 3-year revocation. In her decision, she wrote that for purposes of revocation under CMS law, “convicted” means that a judgment of conviction has been entered by a federal, state, or local court regardless of whether the judgment of conviction has been expunged or otherwise removed. She disagreed with Dr. Maag’s contention that his was a crime against property and, therefore, not akin to any of the felony offenses enumerated under the revocation section, which are crimes against persons.
“Even disregarding the allegations contained in the probable cause affidavit, Petitioner cannot escape the undisputed fact, established by his conviction and his own admissions, that the ‘property’ he so ‘willfully and maliciously’ damaged was a motorcycle traveling at a high rate of speed, and, that two young people were sitting atop that motorcycle,” Judge Hughes wrote. “Moreover, as part of the same conduct, he was charged – and convicted – of misdemeanor reckless driving with ‘willful and wanton disregard for the safety of persons or property.’ Thus, even accepting Petitioner’s description of the events, he unquestionably showed no regard for the safety of the young people on that motorcycle.”
Judge Hughes noted that, although Dr. Maag’s crimes may not be among those specified in the regulation, CMS has broad authority to determine which felonies are detrimental to the best interests of the program and its beneficiaries.
A new career path
Unable to practice emergency medicine and beset with debt, Dr. Maag spiraled into a dark depression. His family had to start using retirement money that he was saving for the future care of his son, who has autism.
“I was suicidal,” he said. “There were two times that I came very close to going out to the woods by my house and hanging myself. All I wanted was to have everything go away. My wife saved my life.”
Slowly, Dr. Maag climbed out of the despondency and began considering new career options. After working and training briefly in hair restoration, Dr. Maag became a hair transplant specialist and opened his own hair restoration practice. It was a way to practice and help patients without having to accept Medicare. Today, he is the founder of Honest Hair Restoration in Bradenton, Fla.
Hair restoration is not the type of medicine that he “was designed to do,” Dr. Maag said, but he has embraced its advantages, such as learning about the business aspects of medicine and having a slower-paced work life. The business, which opened in 2019, is doing well and growing steadily.
Earlier this month, Dr. Maag learned CMS had reinstated his Medicare billing privileges. If an opportunity arises to go back into emergency medicine or urgent care, he is open to the possibilities, he said, but he plans to continue hair restoration for now. He hopes the lessons learned from his road rage incident may help others in similar circumstances.
“If I could go back to that very moment, I would’ve just kept my window up and I wouldn’t have said anything,” Dr. Maag said. “I would’ve kept my mouth shut and gone on about my day. Would I have loved it to have never happened? Yeah, and I’d probably be starting my retirement now. Am I stronger now? Well, I’m probably a hell of a lot wiser. But when all is said and done, I don’t want anybody feeling sorry for me. It was all my doing and I have to live with the consequences.”
Mr. Fayard, the attorney, says the case is a cautionary tale for doctors.
“No one is really above the law,” he said. “There aren’t two legal systems. You can’t just pay a little money and be done. At every level, serious charges have serious ramifications for everyone involved. Law enforcement and judges are not going to care of you’re a physician and you commit a crime. But physicians have a lot more on the line than many others. They can lose their ability to practice.”
A version of this article first appeared on Medscape.com.
Stopping statins linked to death, CV events in elderly
Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.
In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.
Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.
The article was published online June 14, 2021, in JAMA Network Open.
Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.
Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”
The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.
The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.
Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.
Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)
The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.
“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
Findings no surprise
Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.
“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.
Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.
Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.
“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.
Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”
The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.
In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.
Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.
The article was published online June 14, 2021, in JAMA Network Open.
Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.
Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”
The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.
The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.
Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.
Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)
The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.
“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
Findings no surprise
Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.
“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.
Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.
Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.
“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.
Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”
The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Deprescribing may help in reducing inappropriate medication use and adverse events, but for cardiovascular care in the elderly, eliminating statins among patients taking other medications may have negative effects that far outweigh the benefits, a new study suggests.
In a large cohort study, researchers found that the withdrawal of statins from an elderly population receiving polypharmacy was associated with an increase in the risk for hospital admission for heart failure and any cardiovascular outcome, as well as death from any cause.
Statins are “lifesaving” drugs, and “according to the findings of our study, the discontinuation of this therapy has significant effects,” lead study author Federico Rea, PhD, research fellow, Laboratory of Healthcare Research and Pharmacoepidemiology, the department of statistics and quantitative methods, the University of Milano-Bicocca, said in an interview.
The article was published online June 14, 2021, in JAMA Network Open.
Negative clinical consequences, including adverse drug reactions leading to hospitalizations, are causing more physicians to consider deprescribing as a way to reduce problems associated with polypharmacy, the researchers noted.
Statins are “the most widely prescribed medication in the Western world, being a pivotal component in the primary and secondary prevention of cardiovascular (CV) diseases,” they wrote, but because randomized trials usually exclude patients with serious clinical conditions, the precise role statins play for frail patients, such as those with polypharmacy, “is still unclear.”
The population-based cohort study examined 29,047 Italian residents aged 65 years and older who were receiving uninterrupted treatment with statins as well as blood pressure–lowering, antidiabetic, and antiplatelet agents over 16 months. The follow-up period was more than 3 years.
The cohort members were followed to identify those for whom statins were discontinued. Those who continued taking other therapies during the first 6 months after stopping statins were propensity score matched in a 1:1 ratio with patients who did not discontinue taking statins or other drugs. The patient pairs were then followed for fatal and nonfatal outcomes to estimate the risk associated with statin discontinuation.
Of the overall cohort exposed to polypharmacy, 5819 (20.0%) discontinued statins while continuing to take their other medications. Of those, 4,010 were matched with a comparator.
Compared with the maintaining group, those who discontinued statins had the following outcomes: an increased risk for hospital admissions for heart failure (hazard ratio, 1.24; 95% confidence interval, 1.07-1.43), any cardiovascular outcomes (HR, 1.14; 95% CI, 1.03-1.26), death from any cause (HR, 1.15; 95% CI, 1.02-1.30), and emergency admissions for any cause (HR, 1.12; 95% CI, 1.01-1.19)
The increased risk occurred in patients with mild or severe profiles, regardless of gender and whether statins were prescribed as primary or secondary CV prevention.
“We expected that the discontinuation of statins could reduce the risk of access to the emergency department for neurological causes, considered a proxy for the onset of episodes of delirium, [but] this was not observed, suggesting that statin therapy has essential benefits on the reduction of fatal/nonfatal cardiovascular events with no harm effect,” said Dr. Rea, “at least considering major adverse events like hospital and emergency department admissions.”
Findings no surprise
Neil Stone, MD, Bonow Professor of Medicine (Cardiology) and Preventive Medicine at Northwestern University, Chicago, said the study results aren’t surprising.
“Older patients have a higher absolute risk of dying, and withdrawing proven therapy shown to reduce risk of coronary/stroke events in randomized, controlled trials would be expected to result in more cardiovascular events,” Dr. Stone said.
Although polypharmacy is a concern for the elderly and is a factor in decreased adherence, he said better solutions are needed than withdrawing proven, effective therapy. “In that sense, this study indirectly supports more research in the use of polypills to address cardiovascular risk factors,” he said. Giving a single pill that combines medications of proven value in reducing blood pressure and cholesterol might be preferable to reducing the total number of medications.
Given the complexity of polypharmacy, the study investigators say more attention is needed from all health care professionals who care for elderly patients.
“We hope that future studies can shed light on the best way to balance the undeniable benefit of [statins] and the harms, especially among the elderly exposed to polypharmacy,” said Rea.
Further research is also needed into why statins are discontinued in the first place, added Dr. Stone. “We know that statins often are stopped due to symptoms that on further scrutiny may not be related to statin use.”
The study was funded by grants from Fondo d’Ateneo per la Ricerca and Modelling Effectiveness, Cost-effectiveness, and Promoting Health Care Value in the Real World: the Motive Project from the Italian Ministry of the Education, University, and Research. One coauthor served on the advisory board of Roche and has received grants from Bristol Myers Squibb, GlaxoSmithKline, and Novartis outside the submitted work. The other authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Few clinical guidelines exist for treating post-COVID symptoms
As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.
Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.
Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.
which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.
While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.
It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.
One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.
It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.
The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.
Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.
Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.
which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.
While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.
It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.
One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.
It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.
The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
As doctors struggled through several surges of COVID-19 infections, most of what we learned was acquired through real-life experience. While many treatment options were promoted, most flat-out failed to be real therapeutics at all. Now that we have a safe and effective vaccine, we can prevent many infections from this virus. However, we are still left to manage the many post-COVID symptoms our patients continue to suffer with.
Symptoms following infection can last for months and range widely from “brain fog,” fatigue, dyspnea, chest pain, generalized weakness, depression, and a host of others. Patients may experience one or all of these symptoms, and there is currently no good way to predict who will go on to become a COVID “long hauler”.
Following the example of being educated by COVID as it happened, the same is true for managing post-COVID symptoms. The medical community still has a poor understanding of why some people develop it and there are few evidence-based studies to support any treatment modalities.
which they define as “new, recurring, or ongoing symptoms more than 4 weeks after infection, sometimes after initial symptom recovery.” It is important to note that these symptoms can occur in any degree of sickness during the acute infection, including in those who were asymptomatic. Even the actual name of this post-COVID syndrome is still being developed, with several other names being used for it as well.
While the guidelines are quite extensive, the actual clinical recommendations are still vague. For example, it is advised to let the patient know that post-COVID symptoms are still not well understood. While it is important to be transparent with patients, this does little to reassure them. Patients look to doctors, especially their primary care physicians, to guide them on the best treatment paths. Yet, we currently have none for post-COVID syndrome.
It is also advised to treat the patients’ symptoms and help improve functioning. For many diseases, doctors like to get to the root cause of the problem. Treating a symptom often masks an underlying condition. It may make the patient feel better and improve what they are capable of doing, which is important, but it also fails to unmask the real problem. It is also important to note that symptoms can be out of proportion to clinical findings and should not be dismissed: we just don’t have the answers yet.
One helpful recommendation is having a patient keep a diary of their symptoms. This will help both the patient and doctor learn what may be triggering factors. If it is, for example, exertion that induces breathlessness, perhaps the patient can gradually increase their level of activity to minimize symptoms. Additionally, a “comprehensive rehabilitation program” is also advised and this can greatly assist addressing all the issues a patient is experiencing, physically and medically.
It is also advised that management of underlying medical conditions be optimized. While this is very important, it is not something specific to post-COVID syndrome: All patients should have their underlying medical conditions well controlled. It might be that the patient is paying more attention to their overall health, which is a good thing. However, this does not necessarily reduce the current symptoms a patient is experiencing.
The CDC makes a good attempt to offer guidance in the frustrating management of post-COVID syndrome. However, their clinical guidelines fail to offer specific management tools specific to treating post-COVID patients. The recommendations offered are more helpful to health in general. The fact that more specific recommendations are lacking is simply caused by the lack of knowledge of this condition at present. As more research is conducted and more knowledge obtained, new guidelines should become more detailed.
Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].
FDA to add myocarditis warning to mRNA COVID-19 vaccines
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
The Food and Drug Administration is adding a warning to mRNA COVID-19 vaccines’ fact sheets as medical experts continue to investigate cases of heart inflammation, which are rare but are more likely to occur in young men and teen boys.
Doran Fink, MD, PhD, deputy director of the FDA’s division of vaccines and related products applications, told a Centers for Disease Control and Prevention expert panel on June 23 that the FDA is finalizing language on a warning statement for health care providers, vaccine recipients, and parents or caregivers of teens.
The incidents are more likely to follow the second dose of the Pfizer or Moderna vaccine, with chest pain and other symptoms occurring within several days to a week, the warning will note.
“Based on limited follow-up, most cases appear to have been associated with resolution of symptoms, but limited information is available about potential long-term sequelae,” Dr. Fink said, describing the statement to the Advisory Committee on Immunization Practices, independent experts who advise the CDC.
“Symptoms suggestive of myocarditis or pericarditis should result in vaccine recipients seeking medical attention,” he said.
Benefits outweigh risks
Although no formal vote occurred after the meeting, the ACIP members delivered a strong endorsement for continuing to vaccinate 12- to 29-year-olds with the Pfizer and Moderna vaccines despite the warning.
“To me it’s clear, based on current information, that the benefits of vaccine clearly outweigh the risks,” said ACIP member Veronica McNally, president and CEO of the Franny Strong Foundation in Bloomfield, Mich., a sentiment echoed by other members.
As ACIP was meeting, leaders of the nation’s major physician, nurse, and public health associations issued a statement supporting continued vaccination: “The facts are clear: this is an extremely rare side effect, and only an exceedingly small number of people will experience it after vaccination.
“Importantly, for the young people who do, most cases are mild, and individuals recover often on their own or with minimal treatment. In addition, we know that myocarditis and pericarditis are much more common if you get COVID-19, and the risks to the heart from COVID-19 infection can be more severe.”
ACIP heard the evidence behind that claim. According to the Vaccine Safety Datalink, which contains data from more than 12 million medical records, myocarditis or pericarditis occurs in 12- to 39-year-olds at a rate of 8 per 1 million after the second Pfizer dose and 19.8 per 1 million after the second Moderna dose.
The CDC continues to investigate the link between the mRNA vaccines and heart inflammation, including any differences between the vaccines.
Most of the symptoms resolved quickly, said Tom Shimabukuro, deputy director of CDC’s Immunization Safety Office. Of 323 cases analyzed by the CDC, 309 were hospitalized, 295 were discharged, and 218, or 79%, had recovered from symptoms.
“Most postvaccine myocarditis has been responding to minimal treatment,” pediatric cardiologist Matthew Oster, MD, MPH, from Children’s Healthcare of Atlanta, told the panel.
COVID ‘risks are higher’
Overall, the CDC has reported 2,767 COVID-19 deaths among people aged 12-29 years, and there have been 4,018 reported cases of the COVID-linked inflammatory disorder MIS-C since the beginning of the pandemic.
That amounts to 1 MIS-C case in every 3,200 COVID infections – 36% of them among teens aged 12-20 years and 62% among children who are Hispanic or Black and non-Hispanic, according to a CDC presentation.
The CDC estimated that every 1 million second-dose COVID vaccines administered to 12- to 17-year-old boys could prevent 5,700 cases of COVID-19, 215 hospitalizations, 71 ICU admissions, and 2 deaths. There could also be 56-69 myocarditis cases.
The emergence of new variants in the United States and the skewed pattern of vaccination around the country also may increase the risk to unvaccinated young people, noted Grace Lee, MD, MPH, chair of the ACIP’s COVID-19 Vaccine Safety Technical Subgroup and a pediatric infectious disease physician at Stanford (Calif.) Children’s Health.
“If you’re in an area with low vaccination, the risks are higher,” she said. “The benefits [of the vaccine] are going to be far, far greater than any risk.”
Individuals, parents, and their clinicians should consider the full scope of risk when making decisions about vaccination, she said.
As the pandemic evolves, medical experts have to balance the known risks and benefits while they gather more information, said William Schaffner, MD, an infectious disease physician at Vanderbilt University, Nashville, Tenn., and medical director of the National Foundation for Infectious Diseases.
“The story is not over,” Dr. Schaffner said in an interview. “Clearly, we are still working in the face of a pandemic, so there’s urgency to continue vaccinating. But they would like to know more about the long-term consequences of the myocarditis.”
Booster possibilities
Meanwhile, ACIP began conversations on the parameters for a possible vaccine booster. For now, there are simply questions: Would a third vaccine help the immunocompromised gain protection? Should people get a different type of vaccine – mRNA versus adenovirus vector – for their booster? Most important, how long do antibodies last?
“Prior to going around giving everyone boosters, we really need to improve the overall vaccination coverage,” said Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University. “That will protect everyone.”
A version of this article first appeared on Medscape.com.
Gray hair goes away and squids go to space
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Goodbye stress, goodbye gray hair
Last year was a doozy, so it wouldn’t be too surprising if we all had a few new gray strands in our hair. But what if we told you that you don’t need to start dying them or plucking them out? What if they could magically go back to the way they were? Well, it may be possible, sans magic and sans stress.
Investigators recently discovered that the age-old belief that stress will permanently turn your hair gray may not be true after all. There’s a strong possibility that it could turn back to its original color once the stressful agent is eliminated.
“Understanding the mechanisms that allow ‘old’ gray hairs to return to their ‘young’ pigmented states could yield new clues about the malleability of human aging in general and how it is influenced by stress,” said senior author Martin Picard, PhD, of Columbia University, New York.
For the study, 14 volunteers were asked to keep a stress diary and review their levels of stress throughout the week. The researchers used a new method of viewing and capturing the images of tiny parts of the hairs to see how much graying took place in each part of the strand. And what they found – some strands naturally turning back to the original color – had never been documented before.
How did it happen? Our good friend the mitochondria. We haven’t really heard that word since eighth-grade biology, but it’s actually the key link between stress hormones and hair pigmentation. Think of them as little radars picking up all different kinds of signals in your body, like mental/emotional stress. They get a big enough alert and they’re going to react, thus gray hair.
So that’s all it takes? Cut the stress and a full head of gray can go back to brown? Not exactly. The researchers said there may be a “threshold because of biological age and other factors.” They believe middle age is near that threshold and it could easily be pushed over due to stress and could potentially go back. But if you’ve been rocking the salt and pepper or silver fox for a number of years and are looking for change, you might want to just eliminate the stress and pick up a bottle of dye.
One small step for squid
Space does a number on the human body. Forget the obvious like going for a walk outside without a spacesuit, or even the well-known risks like the degradation of bone in microgravity; there are numerous smaller but still important changes to the body during spaceflight, like the disruption of the symbiotic relationship between gut bacteria and the human body. This causes the immune system to lose the ability to recognize threats, and illnesses spread more easily.
Naturally, if astronauts are going to undertake years-long journeys to Mars and beyond, a thorough understanding of this disturbance is necessary, and that’s why NASA has sent a bunch of squid to the International Space Station.
When it comes to animal studies, squid aren’t the usual culprits, but there’s a reason NASA chose calamari over the alternatives: The Hawaiian bobtail squid has a symbiotic relationship with bacteria that regulate their bioluminescence in much the same way that we have a symbiotic relationship with our gut bacteria, but the squid is a much simpler animal. If the bioluminescence-regulating bacteria are disturbed during their time in space, it will be much easier to figure out what’s going wrong.
The experiment is ongoing, but we should salute the brave squid who have taken a giant leap for squidkind. Though if NASA didn’t send them up in a giant bubble, we’re going to be very disappointed.
Less plastic, more vanilla
Have you been racked by guilt over the number of plastic water bottles you use? What about the amount of ice cream you eat? Well, this one’s for you.
Plastic isn’t the first thing you think about when you open up a pint of vanilla ice cream and catch the sweet, spicy vanilla scent, or when you smell those fresh vanilla scones coming out of the oven at the coffee shop, but a new study shows that the flavor of vanilla can come from water bottles.
Here’s the deal. A compound called vanillin is responsible for the scent of vanilla, and it can come naturally from the bean or it can be made synthetically. Believe it or not, 85% of vanillin is made synthetically from fossil fuels!
We’ve definitely grown accustomed to our favorite vanilla scents, foods, and cosmetics. In 2018, the global demand for vanillin was about 40,800 tons and is expected to grow to 65,000 tons by 2025, which far exceeds the supply of natural vanilla.
So what can we do? Well, we can use genetically engineered bacteria to turn plastic water bottles into vanillin, according to a study published in the journal Green Chemistry.
The plastic can be broken down into terephthalic acid, which is very similar, chemically speaking, to vanillin. Similar enough that a bit of bioengineering produced Escherichia coli that could convert the acid into the tasty treat, according to researchers at the University of Edinburgh.
A perfect solution? Decreasing plastic waste while producing a valued food product? The thought of consuming plastic isn’t appetizing, so just eat your ice cream and try to forget about it.
No withdrawals from this bank
Into each life, some milestones must fall: High school graduation, birth of a child, first house, 50th wedding anniversary, COVID-19. One LOTME staffer got really excited – way too excited, actually – when his Nissan Sentra reached 300,000 miles.
Well, there are milestones, and then there are milestones. “1,000 Reasons for Hope” is a report celebrating the first 1,000 brains donated to the VA-BU-CLF Brain Bank. For those of you keeping score at home, that would be the Department of Veterans Affairs, Boston University, and the Concussion Legacy Foundation.
The Brain Bank, created in 2008 to study concussions and chronic traumatic encephalopathy, is the brainchild – yes, we went there – of Chris Nowinski, PhD, a former professional wrestler, and Ann McKee, MD, an expert on neurogenerative disease. “Our discoveries have already inspired changes to sports that will prevent many future cases of CTE in the next generation of athletes,” Dr. Nowinski, the CEO of CLF, said in a written statement.
Data from the first thousand brains show that 706 men, including 305 former NFL players, had football as their primary exposure to head impacts. Women were underrepresented, making up only 2.8% of brain donations, so recruiting females is a priority. Anyone interested in pledging can go to PledgeMyBrain.org or call 617-992-0615 for the 24-hour emergency donation pager.
LOTME wanted to help, so we called the Brain Bank to find out about donating. They asked a few questions and we told them what we do for a living. “Oh, you’re with LOTME? Yeah, we’ve … um, seen that before. It’s, um … funny. Can we put you on hold?” We’re starting to get a little sick of the on-hold music by now.
Clinicians slow to implement lipid-lowering guidelines: GOULD registry
Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.
Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.
“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.
“This is yet another disappointing reminder of how we are failing our patients. Lipid lowering is one of the safest, most effective ways to prevent cardiovascular disease, and yet we are falling short. We have the tools in our toolkit to achieve guideline-based lipid lowering goals, but we just aren’t using them,” said Ann Marie Navar, MD, PhD, associate professor of cardiology at the University of Texas, Dallas.
Patients hesitant
Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.
Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.
The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
Changing guidance
Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.
On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
What’s next
Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.
Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.
Key study results
The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.
The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.
Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.
In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.
Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.
Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.
Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.
Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.
“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.
“This is yet another disappointing reminder of how we are failing our patients. Lipid lowering is one of the safest, most effective ways to prevent cardiovascular disease, and yet we are falling short. We have the tools in our toolkit to achieve guideline-based lipid lowering goals, but we just aren’t using them,” said Ann Marie Navar, MD, PhD, associate professor of cardiology at the University of Texas, Dallas.
Patients hesitant
Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.
Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.
The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
Changing guidance
Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.
On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
What’s next
Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.
Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.
Key study results
The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.
The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.
Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.
In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.
Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.
Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.
Among patients with atherosclerotic cardiovascular disease (ASCVD), 2 years after release of treat-to-target guidelines from the American Heart Association and the European Society of Cardiology and European Atherosclerosis Society, most patients with LDL cholesterol higher than 70 mg/dL did not receive intensification of therapy, and two-thirds continued to have LDL levels above that level, according to a prospective registry study.
Both guidelines recommend driving LDL-C levels to 50% or below of baseline levels; results from the Getting to an Improved Understanding of Low-Density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) registry suggest this is rarely achieved. “Unfortunately it’s not a total surprise, but it’s disappointing,” said Christopher Cannon, MD, the study’s lead author.
“Therapeutic inertia seems to be the rule in clinical practice,” said Jennifer G. Robinson, MD, MPH, who was asked to comment on the study. Dr. Robinson is professor epidemiology and cardiology at the University of Iowa, Iowa City.
“This is yet another disappointing reminder of how we are failing our patients. Lipid lowering is one of the safest, most effective ways to prevent cardiovascular disease, and yet we are falling short. We have the tools in our toolkit to achieve guideline-based lipid lowering goals, but we just aren’t using them,” said Ann Marie Navar, MD, PhD, associate professor of cardiology at the University of Texas, Dallas.
Patients hesitant
Changes in practice following guidelines can often be slow, but in this case may have been complicated by the fact that statins have a reputation for causing side effects, so some patients may be refusing treatment based on what they’ve seen on the Internet. Even though the study looked at all lipid-lowering agents, the misinformation around statins may be spilling over, according to Dr. Cannon. “There’s in general so much misinformation around COVID and every other topic in the world. That makes people question what is real [about] anything,” said Dr. Cannon, a cardiologist at Brigham and Women’s hospital and professor of medicine at Harvard Medical School, both in Boston.
Patient characteristics may partly explain slow uptake. “Clinicians may not think further LDL-C lowering is a high enough priority in terms of potential benefit for a given patient in light of the effort being expended to take care of all their other issues and chronic health problems. If the clinician does bring it up to the patient, there may be barriers in terms of additional medication burden, cost, or acquisition issues,” said Dr. Robinson.
The answer may be better evidence and a more personalized approach. Clinical trials that explore defined patient populations could convince patients of a benefit, and payers to reimburse, according to Dr. Robinson.
Changing guidance
Another complication is that both the guidelines and the field are rapidly changing. The 2013 AHA guidelines did not include a treatment to goal and focused instead on use of high-dose statins. But the 2018 update reversed course after randomized studies demonstrated a benefit to treating to target. The researchers found no increase in the frequency of treating to target after the release of the 2018 guidelines. “Publication and announcement of guidelines doesn’t mean that people are getting treated better. We really have to implement them,” said Dr. Cannon.
On a positive note, the GOULD researchers found high acceptance of the new proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) inhibitors, with over 90% of patients continuing those medications after 2 years. “That’s nice and high. If people do get onto the very intensive lipid-lowing therapies, they tend to stay on them,” said Dr. Cannon.
What’s next
Still, the lack of intensification is concerning, and the findings led to some consternation in Twitter exchanges, said Dr. Cannon. “People posted ‘Well, what do we do now?’ ” Dr. Cannon’s team is addressing the issue with an algorithm-based risk management program with prospective enrollment. They have conducted educational webinars and provided site-specific reports on LDL status among patients at each center compared to others, and hope that information will improve compliance. In 2020, the group published an interim analysis of the first 5,000 enrollees, and Dr. Cannon expects to finish that study by the end of the year.
Dr. Navar agreed that physicians need to do a better job of testing LDL-C levels after treatment to identify patients who require more aggressive therapy. That can be deferred in some primary prevention patients with high LDL-C but normal particle numbers as measured with ApoB. “But in those at high risk for disease and those with established CVD who are not at goal, as long as they don’t have a life-limiting condition, we should always up-titrate therapy. It’s one of the safest, most effective ways to lower cardiovascular risk,” said Dr. Navar.
Key study results
The prospective study included 5,006 patients at 119 centers with a mean age of 68 years. About 40% were women, and 86.1% were White. All had ASCVD and LDL levels of at least 70 mg/dL. After 2 years, 17% had undergone intensification of lipid-lowering therapy (LLT). Among patients with LDL-C levels ≥ 100 mg/dL, 22% underwent LLT intensification, compared with 14% of patients with LDL-C levels of 70-99 mg/dL.
The vast majority, 92%, of patients who underwent LLT via addition of PCSK9 inhibitors were still taking the drug after 2 years.
Three-quarters (3,768) had lipid level measurements at least once during follow-up, and median LDL-C levels dropped from 120 to 95 mg/dL in the ≥100-mg/dL cohort (P < .001), and from 82 to 77 mg/dL in the 70- to 99-mg/dL cohort (P <. 001). There was no significant difference in the median values in the patients on PCSK9 inhibitors.
In all, 21% of the ≥100-mg/dL cohort achieved LDL-C levels <70 mg/dL at 2 years, versus 34% in the 77- to 99-mg/dL cohort and 52% of patients taking PCSK9 inhibitors.
Patients seen at teaching hospitals were more likely to undergo LLT intensification compared to nonteaching hospitals (25% versus 17%; P < .001), as were those where lipid protocols were in place (22% versus 15%; P < .001), and those treated in cardiology (22%) compared to treatment in internal or family medicine (12%; P <.001). The study was published online June 16 in JAMA Cardiology.
Dr. Cannon, Dr. Navar, and Dr. Robinson disclosed ties with Amgen, which funded the study, and other companies.
FROM JAMA CARDIOLOGY