Clinical Endocrinology News

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

Women with repeated attempts at weight loss, even if the weight is regained, have modestly greater weight loss at an obesity management clinic than women without such a history, data suggest.

In a retrospective study of data for more than 11,000 participants in a weight-management program, the frequency of weight loss was significantly correlated with the total lifetime weight loss in men (r = 0.61, P < .0001) and women (r = 0.60, P < .0001).

“It should be harder for you to lose weight when you’re older, as opposed to younger. That’s just biology,” study author Sean Wharton, MD, PharmD, medical director of the Wharton Medical Clinic, Burlington, Ont., told this news organization. But older people “have practiced a whole lot more than younger people. That’s probably one of the big things” in their favor, he added.

Dr. Wharton also is a clinical adjunct professor at York University, Toronto, and the lead author of 2020 Canadian clinical practice guidelines on obesity.

The current data were published in Obesity.
 

Practice makes perfect?

The prevalence of obesity is increasing. It is uncertain whether frequent weight losses help or hinder future weight-loss attempts. The effect of age at overweight on future weight loss attempts is also unclear.

To examine these questions, the current researchers analyzed the experiences of patients with obesity treated at the Wharton Medical Clinic Weight Management Program, Hamilton, Ont. At enrollment, participants responded to a questionnaire that elicited information about basic demographics, past weight loss and health practices, medical history, and family medical history. Patients did not receive any stipend for their participation and consented to the use of their medical data for research purposes. The investigators assessed weight change through a retrospective review of electronic medical records.

The study examined a data set that included 36,124 patients who were predominantly White, middle-aged women. “Although this is reflective of the demographic that is most commonly seeking obesity management in North America, the applicability of these findings to other groups is unclear,” wrote the investigators.

As a group, women under age 40 lost 1.7 kg, while those from ages 40 to 60 lost 3.2 kg, and women older than 60 lost 4.2 kg. Weight loss among men was greater and followed a similar pattern. Men under age 40 lost 3.0 kg, those between ages 40 and 60 lost 4.2 kg, and those older than 60 lost 5.2 kg.

To examine how long participants had been trying to lose weight, the investigators analyzed their age of overweight onset. Most participants reported having become overweight before age 40 and having lost at least 4.5 kg at least once in their lifetime. Older women with a longer history of losing weight had better results during the study.

In middle-aged and older women, but not men or younger women, earlier age of overweight onset and lifetime weight loss were associated with modestly greater weight loss at the clinic. When the researchers assessed women age 60 and older, they found that those who had an age of overweight onset before age 10 lost 4.9 kg on average, while those whose age of overweight onset was between ages 20 and 39 lost 4.3 kg. Women with an age of overweight onset above 40 had a weight loss of 3.5 kg.

The finding of greater weight loss in older women who were experienced in dieting was surprising, said Dr. Wharton. It may reflect the effects of perseverance and lifestyle changes. “The other thing is that [older women] also have more time. They have more availability. They make more appointments. They have the ability to be more focused,” said Dr. Wharton.

The Wharton Medical Clinic operates within the Ontario Health Insurance Plan, and all services are provided at no charge to the patient, which may reduce the selection bias against patients with low socioeconomic status, wrote the investigators.
 

Inclusive population

Lesley D. Lutes, PhD, director of the Center for Obesity and Well-Being Research Excellence (CORE) at the University of British Columbia, Vancouver, said that one of its strengths was its reflection of real-world experience.

Too often, study populations do not reflect well the experiences of people battling obesity, she added. Many potential participants are excluded because of common medical comorbidities such as heart conditions. “So, you don’t see the real-world outcomes for the majority of people” from these studies, said Dr. Lutes.

Furthermore, researchers sometimes draw conclusions about obesity based on data that draws from only a “tiny slice” of the group of patients who can qualify for studies, she added. The resulting recommendations may not suit most patients.

In contrast, the current research was based on a more inclusive set of patient data. “That was an incredible strength of this study, that there [were] no exclusionary criteria” in terms of medical conditions, she said.

No outside funding for the study was reported. Dr. Wharton is the medical director of the Wharton Medical Clinic.

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

It’s not a new drug – it’s been available in topical form for hair loss since 1988 and was approved as an antihypertensive in 1979 – but a low-dose oral form of minoxidil is gaining new currency – and a growing public profile – as an adjunctive therapy for hair loss.

The number of scholarly publications examining its use for hair loss has grown dramatically in the last 2 years: There were 2 in 2019, and that jumped to 17 in 2020 and 20 in 2021, with another 16 published so far this year, according to a PubMed search. An August article in The New York Times touting it as a potential cheap magic bullet is likely to drum up even more interest, said dermatologists.

The low-dose formulation is especially exciting for women, as there have been few great oral options for them, clinicians said.

Female hair loss “is devastating,” said Lily Talakoub, MD, adding that topical minoxidil (Rogaine), topical serums, and supplements “really do not provide the considerable growth that women really want to see.” Oral minoxidil is not approved by the U.S. Food and Drug Administration for hair loss, but “it has been shown in studies to cause the hairs to grow,” and has become a “lifeline” for women, said Dr. Talakoub, a dermatologist who is in private practice in McLean, Va.

“For many years we haven’t had anything new to tell patients medically,” said Lynne J. Goldberg, MD, professor of dermatology and pathology at Boston University School of Medicine. “Now, all of the sudden there’s a cheap, widely available efficacious medicine. That’s huge for female-pattern hair loss,” said Dr. Goldberg, who is also the director of the Boston Medical Center’s Hair Clinic.

“I’ve been using oral minoxidil for about 4 years with great success,” said dermatologist Eva Simmons-O’Brien, MD, who is in private practice in Towson, Md. She has used it primarily in women, mainly because she sees more women than men for hair loss.

Dr. Simmons-O’Brien said the excitement about low-dose oral minoxidil follows an increasing recognition in the medical and scientific community that hair loss is more than just a cosmetic issue.
 

Mechanism not fully understood

When minoxidil was first brought to market as an antihypertensive, clinicians noted hair growth in “balding patients,” which led to the development of the topical form. Even though it has been used for hair growth for decades, its mechanism of action is not fully understood. It is known that minoxidil is a vasodilator; it may also increase DNA synthesis and enhance cell proliferation, according to a review published in 2019.

“The positive effect of minoxidil on hair growth is mainly due to its metabolite, minoxidil sulfate, and the enzyme responsible for this conversion is sulfotransferase, which is located in hair follicles and varies in production among individuals,” write the authors, all affiliated with Mahidol University in Bangkok, Thailand.

Writing in the American Academy of Dermatology’s Dermatology World Insights and Inquiries, Warren R. Heymann, MD, observed that “even after decades of use,” how minoxidil improves alopecia is still not completely understood. He noted that a 2020 review found that minoxidil’s vasodilatory effects “are propagated by upregulation of vascular endothelial growth factor (VEGF), increasing cutaneous blood flow with resultant increase in oxygen and growth factor delivery to the hair follicle.” The medication prolongs the anagen phase and shortens the telogen phase, added Dr. Heymann, head of dermatology at Rowan University, Camden, N.J.

As an antihypertensive, minoxidil is given at 5-40 mg daily. Those doses have produced serious side effects such as sodium and fluid retention, ischemic heart disease, pericardial effusion, and pulmonary hypertension, according to the Thai researchers.

Those side effects have appeared to be rare with low-dose oral minoxidil. However, in JAAD Case Reports, South African researchers reported a case in which low-dose oral minoxidil may have led to cardiac side effects. A healthy 40-year-old woman, who after 3 weeks of treatment with 5% topical minoxidil, tacrolimus ointment 0.1%, clobetasol propionate ointment, 100 mg of doxycycline twice daily, and 0.25 mg of oral minoxidil daily, was hospitalized with full-body edema. An ultrasound showed fluid collections in the pericardium, pleural space, and abdomen. She also had a pleural effusion. The patient was given 40 mg of intravenous furosemide daily for 4 days, and the edema resolved.

“Having excluded other causes of pericardial effusion and anasarca in the previously healthy, young woman, we concluded that LDOM [low-dose oral minoxidil] was responsible for her clinical presentation,” write the authors.

A review of 17 studies published on-line in 2020 in the Journal of the American Academy of Dermatology found low-dose minoxidil to be safe and effective. Androgenetic alopecia was the most commonly studied, with doses of 0.25-1.25 mg proving to be effective and safe. It was also safe and effective for female-pattern hair loss, traction alopecia, chronic telogen effluvium, lichen planopilaris, alopecia areata, and permanent chemotherapy-induced alopecia.

The most common adverse effect was hypertrichosis. Other adverse events included postural hypotension and dizziness, lower-limb edema, and mild blood pressure changes.

In another multicenter, 1,404-patient safety study published in 2021 in JAAD, the authors found that hypertrichosis was the most frequent adverse event, reported by 15% of patients. Systemic adverse events included lightheadedness (1.7% of patients), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%). Only 29 patients (1.2%) withdrew because of these side effects.

“It definitely helps, and it’s relatively safe,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University in Washington. “But I wouldn’t want to call it a game-changer,” he said, adding that it works best when used in combination with other therapies. He often uses it with a 5-alpha reductase inhibitor – finasteride (Propecia) or dutasteride (Avodart) – “rather than as a monotherapy,” said Dr. Friedman.
 

From Australia to around the globe

The first publication on low-dose oral minoxidil for hair loss was in December 2017. The pilot study in female-pattern hair loss was published in the International Journal of Dermatology by Rodney Sinclair, MBBS, MD, a Melbourne, Australia–based dermatologist.

Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she first heard Dr. Sinclair present his findings at an alopecia research meeting in Japan shortly before his initial publication.

“After that, I think all of us said, ‘Huh, this is interesting, and let’s try it, because we’re always looking for something more to help our patients,’” Dr. McMichael said, adding that she’s been prescribing low-dose minoxidil to her patients for 5 years.

She and colleagues at Wake Forest, along with Jerry Cooley, MD, a dermatologist in private practice in Charlotte, published a retrospective case series in March, looking at 105 adult patients – 80 women (ages 24-80) and 25 men (ages 19-63) – who were treated for androgenetic alopecia and/or telogen effluvium with oral minoxidil (dose range of 0.625–2.5 mg) once daily for a year, matched to 105 case controls.

Efficacy was based on the clinician’s assessment of clinical response and clinical photographic evaluation using a 3-point scale (worsening, stabilization, and improvement). Half of those treated demonstrated clinical improvement and 43% demonstrated stabilization. There was a significant difference (P < .001) in clinical response between those who received minoxidil and the controls.

Ideal patients?

Given its ease of use and low cost – $4-$12 for a 30-day supply of 2.5 mg tablets, according to GoodRX – low-dose minoxidil is a good fit for many patients, said dermatologists.

The best candidate is “a woman who’s perimenopausal or menopausal who’s got what we would say is moderate to severe loss of hair that’s kind of just starting,” said Dr. Simmons-O’Brien. The medication is not likely to grow hair where there is scarring already, however, she said.

“I tend to use it in people who either don’t want to do the topical minoxidil or have used it and have a lot of potential side effects from it,” like itching and irritation, said Dr. McMichael. She said oral minoxidil can also be helpful as an adjunct in patients with alopecia areata and that it can be used after anti-inflammatory treatments in central centrifugal cicatricial alopecia.

Dr. Goldberg said low-dose minoxidil would not be her first choice for female-pattern hair loss but that it’s “a great alternative” for people who can’t tolerate the topical form. Most of the women she has prescribed it to “have been pretty happy,” she added.

“I would be a little cautious in patients on a number of other medications,” Dr. Goldberg said, noting minoxidil’s potential systemic side effects.

Clinicians said they generally consult with a patient’s internist when they are starting them on oral minoxidil. “I always want to touch base with the primary care physician first,” said Dr. Friedman.

“If they’re on oral antihypertensive medications already, then I would ask them to talk to either their primary care physician or their cardiologist to make sure it’s okay to give this low dose,” said Dr. McMichael.

At the low doses, minoxidil rarely has any blood pressure–lowering effects, dermatologists said.

Women are usually started on 1.25 mg, while men can start at a higher, 2.5-mg dose, said clinicians.

Dr. Goldberg and Dr. Simmons-O’Brien said that recent additional warnings for finasteride about sexual side effects and the potential for suicide have changed the way they approach its use in young men, and that it has highlighted the potential for oral minoxidil as an alternative.

Oral minoxidil is rarely used as a monotherapy. “It takes a village” to address hair loss, said Dr. Simmons-O’Brien, noting that she likes to evaluate nutrition, vitamin D levels, and whether a patient is anemic or has thyroid disease when determining a course of action.

Dermatologists said they use oral minoxidil in combination with spironolactone, topical minoxidil, finasteride, or dutasteride. If patients are already on antihypertensives or at risk for excessive blood pressure–lowering effects of a combination that includes spironolactone, the dermatologists said again they will consult with a patient’s primary care physician first.

For women, the main limiting factor with oral minoxidil may be unwanted hair growth, usually on the face. Most of the clinicians interviewed for this story said they did not use spironolactone to counteract that hypertrichosis.

Dr. McMichael said she cautions African American women or women of African descent – who tend to have more body hair at baseline – that they should be aware of the potential for excess hair growth associated with low-dose minoxidil. She and other dermatologists interviewed for this story said they urge patients who are bothered by the excess hair to shave or wax or use other nonpharmacologic approaches.

The excess hair growth is less bothersome for men, they said.
 

Not a magic wand

Despite the increased profile and interest, oral minoxidil is not a cure-all, clinicians said.

“It’s important for patients to realize that hair loss can be complicated and there is no one magic wand,” said Dr. Simmons-O’Brien. Clinicians typically “are using several things to help encourage these follicular units to not miniaturize and disappear and create scars,” she said.

Dr. Friedman said he finds that patients have a hard time hearing that to continue to maintain growth, they have to take a medication for the rest of their life. “If you stop, you will have to start again,” he said. 

Oral minoxidil, when used in combination with other therapies, will improve hair growth, said Dr. Goldberg. But it will not take someone back a decade, she said. “I try to temper expectations – promise a little and achieve more,” Dr. Goldberg said.

The study was independently supported. Dr. Smith and Dr. Jones report no relevant financial relationships. Dr. Simmons-O’Brien reports that she has received speaking fees from Isdin. Dr. McMichael disclosed relationships with Eli Lilly, Pfizer, Nutrafol, Revian, and UCB Pharma. Dr. Friedman, Dr. Goldberg, and Dr. Talakoub reported no disclosures.

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

It’s not a new drug – it’s been available in topical form for hair loss since 1988 and was approved as an antihypertensive in 1979 – but a low-dose oral form of minoxidil is gaining new currency – and a growing public profile – as an adjunctive therapy for hair loss.

The number of scholarly publications examining its use for hair loss has grown dramatically in the last 2 years: There were 2 in 2019, and that jumped to 17 in 2020 and 20 in 2021, with another 16 published so far this year, according to a PubMed search. An August article in The New York Times touting it as a potential cheap magic bullet is likely to drum up even more interest, said dermatologists.

The low-dose formulation is especially exciting for women, as there have been few great oral options for them, clinicians said.

Female hair loss “is devastating,” said Lily Talakoub, MD, adding that topical minoxidil (Rogaine), topical serums, and supplements “really do not provide the considerable growth that women really want to see.” Oral minoxidil is not approved by the U.S. Food and Drug Administration for hair loss, but “it has been shown in studies to cause the hairs to grow,” and has become a “lifeline” for women, said Dr. Talakoub, a dermatologist who is in private practice in McLean, Va.

“For many years we haven’t had anything new to tell patients medically,” said Lynne J. Goldberg, MD, professor of dermatology and pathology at Boston University School of Medicine. “Now, all of the sudden there’s a cheap, widely available efficacious medicine. That’s huge for female-pattern hair loss,” said Dr. Goldberg, who is also the director of the Boston Medical Center’s Hair Clinic.

“I’ve been using oral minoxidil for about 4 years with great success,” said dermatologist Eva Simmons-O’Brien, MD, who is in private practice in Towson, Md. She has used it primarily in women, mainly because she sees more women than men for hair loss.

Dr. Simmons-O’Brien said the excitement about low-dose oral minoxidil follows an increasing recognition in the medical and scientific community that hair loss is more than just a cosmetic issue.
 

Mechanism not fully understood

When minoxidil was first brought to market as an antihypertensive, clinicians noted hair growth in “balding patients,” which led to the development of the topical form. Even though it has been used for hair growth for decades, its mechanism of action is not fully understood. It is known that minoxidil is a vasodilator; it may also increase DNA synthesis and enhance cell proliferation, according to a review published in 2019.

“The positive effect of minoxidil on hair growth is mainly due to its metabolite, minoxidil sulfate, and the enzyme responsible for this conversion is sulfotransferase, which is located in hair follicles and varies in production among individuals,” write the authors, all affiliated with Mahidol University in Bangkok, Thailand.

Writing in the American Academy of Dermatology’s Dermatology World Insights and Inquiries, Warren R. Heymann, MD, observed that “even after decades of use,” how minoxidil improves alopecia is still not completely understood. He noted that a 2020 review found that minoxidil’s vasodilatory effects “are propagated by upregulation of vascular endothelial growth factor (VEGF), increasing cutaneous blood flow with resultant increase in oxygen and growth factor delivery to the hair follicle.” The medication prolongs the anagen phase and shortens the telogen phase, added Dr. Heymann, head of dermatology at Rowan University, Camden, N.J.

As an antihypertensive, minoxidil is given at 5-40 mg daily. Those doses have produced serious side effects such as sodium and fluid retention, ischemic heart disease, pericardial effusion, and pulmonary hypertension, according to the Thai researchers.

Those side effects have appeared to be rare with low-dose oral minoxidil. However, in JAAD Case Reports, South African researchers reported a case in which low-dose oral minoxidil may have led to cardiac side effects. A healthy 40-year-old woman, who after 3 weeks of treatment with 5% topical minoxidil, tacrolimus ointment 0.1%, clobetasol propionate ointment, 100 mg of doxycycline twice daily, and 0.25 mg of oral minoxidil daily, was hospitalized with full-body edema. An ultrasound showed fluid collections in the pericardium, pleural space, and abdomen. She also had a pleural effusion. The patient was given 40 mg of intravenous furosemide daily for 4 days, and the edema resolved.

“Having excluded other causes of pericardial effusion and anasarca in the previously healthy, young woman, we concluded that LDOM [low-dose oral minoxidil] was responsible for her clinical presentation,” write the authors.

A review of 17 studies published on-line in 2020 in the Journal of the American Academy of Dermatology found low-dose minoxidil to be safe and effective. Androgenetic alopecia was the most commonly studied, with doses of 0.25-1.25 mg proving to be effective and safe. It was also safe and effective for female-pattern hair loss, traction alopecia, chronic telogen effluvium, lichen planopilaris, alopecia areata, and permanent chemotherapy-induced alopecia.

The most common adverse effect was hypertrichosis. Other adverse events included postural hypotension and dizziness, lower-limb edema, and mild blood pressure changes.

In another multicenter, 1,404-patient safety study published in 2021 in JAAD, the authors found that hypertrichosis was the most frequent adverse event, reported by 15% of patients. Systemic adverse events included lightheadedness (1.7% of patients), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%). Only 29 patients (1.2%) withdrew because of these side effects.

“It definitely helps, and it’s relatively safe,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University in Washington. “But I wouldn’t want to call it a game-changer,” he said, adding that it works best when used in combination with other therapies. He often uses it with a 5-alpha reductase inhibitor – finasteride (Propecia) or dutasteride (Avodart) – “rather than as a monotherapy,” said Dr. Friedman.
 

From Australia to around the globe

The first publication on low-dose oral minoxidil for hair loss was in December 2017. The pilot study in female-pattern hair loss was published in the International Journal of Dermatology by Rodney Sinclair, MBBS, MD, a Melbourne, Australia–based dermatologist.

Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she first heard Dr. Sinclair present his findings at an alopecia research meeting in Japan shortly before his initial publication.

“After that, I think all of us said, ‘Huh, this is interesting, and let’s try it, because we’re always looking for something more to help our patients,’” Dr. McMichael said, adding that she’s been prescribing low-dose minoxidil to her patients for 5 years.

She and colleagues at Wake Forest, along with Jerry Cooley, MD, a dermatologist in private practice in Charlotte, published a retrospective case series in March, looking at 105 adult patients – 80 women (ages 24-80) and 25 men (ages 19-63) – who were treated for androgenetic alopecia and/or telogen effluvium with oral minoxidil (dose range of 0.625–2.5 mg) once daily for a year, matched to 105 case controls.

Efficacy was based on the clinician’s assessment of clinical response and clinical photographic evaluation using a 3-point scale (worsening, stabilization, and improvement). Half of those treated demonstrated clinical improvement and 43% demonstrated stabilization. There was a significant difference (P < .001) in clinical response between those who received minoxidil and the controls.

Ideal patients?

Given its ease of use and low cost – $4-$12 for a 30-day supply of 2.5 mg tablets, according to GoodRX – low-dose minoxidil is a good fit for many patients, said dermatologists.

The best candidate is “a woman who’s perimenopausal or menopausal who’s got what we would say is moderate to severe loss of hair that’s kind of just starting,” said Dr. Simmons-O’Brien. The medication is not likely to grow hair where there is scarring already, however, she said.

“I tend to use it in people who either don’t want to do the topical minoxidil or have used it and have a lot of potential side effects from it,” like itching and irritation, said Dr. McMichael. She said oral minoxidil can also be helpful as an adjunct in patients with alopecia areata and that it can be used after anti-inflammatory treatments in central centrifugal cicatricial alopecia.

Dr. Goldberg said low-dose minoxidil would not be her first choice for female-pattern hair loss but that it’s “a great alternative” for people who can’t tolerate the topical form. Most of the women she has prescribed it to “have been pretty happy,” she added.

“I would be a little cautious in patients on a number of other medications,” Dr. Goldberg said, noting minoxidil’s potential systemic side effects.

Clinicians said they generally consult with a patient’s internist when they are starting them on oral minoxidil. “I always want to touch base with the primary care physician first,” said Dr. Friedman.

“If they’re on oral antihypertensive medications already, then I would ask them to talk to either their primary care physician or their cardiologist to make sure it’s okay to give this low dose,” said Dr. McMichael.

At the low doses, minoxidil rarely has any blood pressure–lowering effects, dermatologists said.

Women are usually started on 1.25 mg, while men can start at a higher, 2.5-mg dose, said clinicians.

Dr. Goldberg and Dr. Simmons-O’Brien said that recent additional warnings for finasteride about sexual side effects and the potential for suicide have changed the way they approach its use in young men, and that it has highlighted the potential for oral minoxidil as an alternative.

Oral minoxidil is rarely used as a monotherapy. “It takes a village” to address hair loss, said Dr. Simmons-O’Brien, noting that she likes to evaluate nutrition, vitamin D levels, and whether a patient is anemic or has thyroid disease when determining a course of action.

Dermatologists said they use oral minoxidil in combination with spironolactone, topical minoxidil, finasteride, or dutasteride. If patients are already on antihypertensives or at risk for excessive blood pressure–lowering effects of a combination that includes spironolactone, the dermatologists said again they will consult with a patient’s primary care physician first.

For women, the main limiting factor with oral minoxidil may be unwanted hair growth, usually on the face. Most of the clinicians interviewed for this story said they did not use spironolactone to counteract that hypertrichosis.

Dr. McMichael said she cautions African American women or women of African descent – who tend to have more body hair at baseline – that they should be aware of the potential for excess hair growth associated with low-dose minoxidil. She and other dermatologists interviewed for this story said they urge patients who are bothered by the excess hair to shave or wax or use other nonpharmacologic approaches.

The excess hair growth is less bothersome for men, they said.
 

Not a magic wand

Despite the increased profile and interest, oral minoxidil is not a cure-all, clinicians said.

“It’s important for patients to realize that hair loss can be complicated and there is no one magic wand,” said Dr. Simmons-O’Brien. Clinicians typically “are using several things to help encourage these follicular units to not miniaturize and disappear and create scars,” she said.

Dr. Friedman said he finds that patients have a hard time hearing that to continue to maintain growth, they have to take a medication for the rest of their life. “If you stop, you will have to start again,” he said. 

Oral minoxidil, when used in combination with other therapies, will improve hair growth, said Dr. Goldberg. But it will not take someone back a decade, she said. “I try to temper expectations – promise a little and achieve more,” Dr. Goldberg said.

The study was independently supported. Dr. Smith and Dr. Jones report no relevant financial relationships. Dr. Simmons-O’Brien reports that she has received speaking fees from Isdin. Dr. McMichael disclosed relationships with Eli Lilly, Pfizer, Nutrafol, Revian, and UCB Pharma. Dr. Friedman, Dr. Goldberg, and Dr. Talakoub reported no disclosures.

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

It’s not a new drug – it’s been available in topical form for hair loss since 1988 and was approved as an antihypertensive in 1979 – but a low-dose oral form of minoxidil is gaining new currency – and a growing public profile – as an adjunctive therapy for hair loss.

The number of scholarly publications examining its use for hair loss has grown dramatically in the last 2 years: There were 2 in 2019, and that jumped to 17 in 2020 and 20 in 2021, with another 16 published so far this year, according to a PubMed search. An August article in The New York Times touting it as a potential cheap magic bullet is likely to drum up even more interest, said dermatologists.

The low-dose formulation is especially exciting for women, as there have been few great oral options for them, clinicians said.

Female hair loss “is devastating,” said Lily Talakoub, MD, adding that topical minoxidil (Rogaine), topical serums, and supplements “really do not provide the considerable growth that women really want to see.” Oral minoxidil is not approved by the U.S. Food and Drug Administration for hair loss, but “it has been shown in studies to cause the hairs to grow,” and has become a “lifeline” for women, said Dr. Talakoub, a dermatologist who is in private practice in McLean, Va.

“For many years we haven’t had anything new to tell patients medically,” said Lynne J. Goldberg, MD, professor of dermatology and pathology at Boston University School of Medicine. “Now, all of the sudden there’s a cheap, widely available efficacious medicine. That’s huge for female-pattern hair loss,” said Dr. Goldberg, who is also the director of the Boston Medical Center’s Hair Clinic.

“I’ve been using oral minoxidil for about 4 years with great success,” said dermatologist Eva Simmons-O’Brien, MD, who is in private practice in Towson, Md. She has used it primarily in women, mainly because she sees more women than men for hair loss.

Dr. Simmons-O’Brien said the excitement about low-dose oral minoxidil follows an increasing recognition in the medical and scientific community that hair loss is more than just a cosmetic issue.
 

Mechanism not fully understood

When minoxidil was first brought to market as an antihypertensive, clinicians noted hair growth in “balding patients,” which led to the development of the topical form. Even though it has been used for hair growth for decades, its mechanism of action is not fully understood. It is known that minoxidil is a vasodilator; it may also increase DNA synthesis and enhance cell proliferation, according to a review published in 2019.

“The positive effect of minoxidil on hair growth is mainly due to its metabolite, minoxidil sulfate, and the enzyme responsible for this conversion is sulfotransferase, which is located in hair follicles and varies in production among individuals,” write the authors, all affiliated with Mahidol University in Bangkok, Thailand.

Writing in the American Academy of Dermatology’s Dermatology World Insights and Inquiries, Warren R. Heymann, MD, observed that “even after decades of use,” how minoxidil improves alopecia is still not completely understood. He noted that a 2020 review found that minoxidil’s vasodilatory effects “are propagated by upregulation of vascular endothelial growth factor (VEGF), increasing cutaneous blood flow with resultant increase in oxygen and growth factor delivery to the hair follicle.” The medication prolongs the anagen phase and shortens the telogen phase, added Dr. Heymann, head of dermatology at Rowan University, Camden, N.J.

As an antihypertensive, minoxidil is given at 5-40 mg daily. Those doses have produced serious side effects such as sodium and fluid retention, ischemic heart disease, pericardial effusion, and pulmonary hypertension, according to the Thai researchers.

Those side effects have appeared to be rare with low-dose oral minoxidil. However, in JAAD Case Reports, South African researchers reported a case in which low-dose oral minoxidil may have led to cardiac side effects. A healthy 40-year-old woman, who after 3 weeks of treatment with 5% topical minoxidil, tacrolimus ointment 0.1%, clobetasol propionate ointment, 100 mg of doxycycline twice daily, and 0.25 mg of oral minoxidil daily, was hospitalized with full-body edema. An ultrasound showed fluid collections in the pericardium, pleural space, and abdomen. She also had a pleural effusion. The patient was given 40 mg of intravenous furosemide daily for 4 days, and the edema resolved.

“Having excluded other causes of pericardial effusion and anasarca in the previously healthy, young woman, we concluded that LDOM [low-dose oral minoxidil] was responsible for her clinical presentation,” write the authors.

A review of 17 studies published on-line in 2020 in the Journal of the American Academy of Dermatology found low-dose minoxidil to be safe and effective. Androgenetic alopecia was the most commonly studied, with doses of 0.25-1.25 mg proving to be effective and safe. It was also safe and effective for female-pattern hair loss, traction alopecia, chronic telogen effluvium, lichen planopilaris, alopecia areata, and permanent chemotherapy-induced alopecia.

The most common adverse effect was hypertrichosis. Other adverse events included postural hypotension and dizziness, lower-limb edema, and mild blood pressure changes.

In another multicenter, 1,404-patient safety study published in 2021 in JAAD, the authors found that hypertrichosis was the most frequent adverse event, reported by 15% of patients. Systemic adverse events included lightheadedness (1.7% of patients), fluid retention (1.3%), tachycardia (0.9%), headache (0.4%), periorbital edema (0.3%), and insomnia (0.2%). Only 29 patients (1.2%) withdrew because of these side effects.

“It definitely helps, and it’s relatively safe,” said Adam Friedman, MD, professor and chair of dermatology at George Washington University in Washington. “But I wouldn’t want to call it a game-changer,” he said, adding that it works best when used in combination with other therapies. He often uses it with a 5-alpha reductase inhibitor – finasteride (Propecia) or dutasteride (Avodart) – “rather than as a monotherapy,” said Dr. Friedman.
 

From Australia to around the globe

The first publication on low-dose oral minoxidil for hair loss was in December 2017. The pilot study in female-pattern hair loss was published in the International Journal of Dermatology by Rodney Sinclair, MBBS, MD, a Melbourne, Australia–based dermatologist.

Amy McMichael, MD, professor of dermatology at Wake Forest University, Winston-Salem, N.C., said she first heard Dr. Sinclair present his findings at an alopecia research meeting in Japan shortly before his initial publication.

“After that, I think all of us said, ‘Huh, this is interesting, and let’s try it, because we’re always looking for something more to help our patients,’” Dr. McMichael said, adding that she’s been prescribing low-dose minoxidil to her patients for 5 years.

She and colleagues at Wake Forest, along with Jerry Cooley, MD, a dermatologist in private practice in Charlotte, published a retrospective case series in March, looking at 105 adult patients – 80 women (ages 24-80) and 25 men (ages 19-63) – who were treated for androgenetic alopecia and/or telogen effluvium with oral minoxidil (dose range of 0.625–2.5 mg) once daily for a year, matched to 105 case controls.

Efficacy was based on the clinician’s assessment of clinical response and clinical photographic evaluation using a 3-point scale (worsening, stabilization, and improvement). Half of those treated demonstrated clinical improvement and 43% demonstrated stabilization. There was a significant difference (P < .001) in clinical response between those who received minoxidil and the controls.

Ideal patients?

Given its ease of use and low cost – $4-$12 for a 30-day supply of 2.5 mg tablets, according to GoodRX – low-dose minoxidil is a good fit for many patients, said dermatologists.

The best candidate is “a woman who’s perimenopausal or menopausal who’s got what we would say is moderate to severe loss of hair that’s kind of just starting,” said Dr. Simmons-O’Brien. The medication is not likely to grow hair where there is scarring already, however, she said.

“I tend to use it in people who either don’t want to do the topical minoxidil or have used it and have a lot of potential side effects from it,” like itching and irritation, said Dr. McMichael. She said oral minoxidil can also be helpful as an adjunct in patients with alopecia areata and that it can be used after anti-inflammatory treatments in central centrifugal cicatricial alopecia.

Dr. Goldberg said low-dose minoxidil would not be her first choice for female-pattern hair loss but that it’s “a great alternative” for people who can’t tolerate the topical form. Most of the women she has prescribed it to “have been pretty happy,” she added.

“I would be a little cautious in patients on a number of other medications,” Dr. Goldberg said, noting minoxidil’s potential systemic side effects.

Clinicians said they generally consult with a patient’s internist when they are starting them on oral minoxidil. “I always want to touch base with the primary care physician first,” said Dr. Friedman.

“If they’re on oral antihypertensive medications already, then I would ask them to talk to either their primary care physician or their cardiologist to make sure it’s okay to give this low dose,” said Dr. McMichael.

At the low doses, minoxidil rarely has any blood pressure–lowering effects, dermatologists said.

Women are usually started on 1.25 mg, while men can start at a higher, 2.5-mg dose, said clinicians.

Dr. Goldberg and Dr. Simmons-O’Brien said that recent additional warnings for finasteride about sexual side effects and the potential for suicide have changed the way they approach its use in young men, and that it has highlighted the potential for oral minoxidil as an alternative.

Oral minoxidil is rarely used as a monotherapy. “It takes a village” to address hair loss, said Dr. Simmons-O’Brien, noting that she likes to evaluate nutrition, vitamin D levels, and whether a patient is anemic or has thyroid disease when determining a course of action.

Dermatologists said they use oral minoxidil in combination with spironolactone, topical minoxidil, finasteride, or dutasteride. If patients are already on antihypertensives or at risk for excessive blood pressure–lowering effects of a combination that includes spironolactone, the dermatologists said again they will consult with a patient’s primary care physician first.

For women, the main limiting factor with oral minoxidil may be unwanted hair growth, usually on the face. Most of the clinicians interviewed for this story said they did not use spironolactone to counteract that hypertrichosis.

Dr. McMichael said she cautions African American women or women of African descent – who tend to have more body hair at baseline – that they should be aware of the potential for excess hair growth associated with low-dose minoxidil. She and other dermatologists interviewed for this story said they urge patients who are bothered by the excess hair to shave or wax or use other nonpharmacologic approaches.

The excess hair growth is less bothersome for men, they said.
 

Not a magic wand

Despite the increased profile and interest, oral minoxidil is not a cure-all, clinicians said.

“It’s important for patients to realize that hair loss can be complicated and there is no one magic wand,” said Dr. Simmons-O’Brien. Clinicians typically “are using several things to help encourage these follicular units to not miniaturize and disappear and create scars,” she said.

Dr. Friedman said he finds that patients have a hard time hearing that to continue to maintain growth, they have to take a medication for the rest of their life. “If you stop, you will have to start again,” he said. 

Oral minoxidil, when used in combination with other therapies, will improve hair growth, said Dr. Goldberg. But it will not take someone back a decade, she said. “I try to temper expectations – promise a little and achieve more,” Dr. Goldberg said.

The study was independently supported. Dr. Smith and Dr. Jones report no relevant financial relationships. Dr. Simmons-O’Brien reports that she has received speaking fees from Isdin. Dr. McMichael disclosed relationships with Eli Lilly, Pfizer, Nutrafol, Revian, and UCB Pharma. Dr. Friedman, Dr. Goldberg, and Dr. Talakoub reported no disclosures.

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I run the division of medical ethics at New York University Grossman School of Medicine.

Many of you know that President Biden created a loan forgiveness program, forgiving up to $10,000 against federal student loans, including graduate and undergraduate education. The Department of Education is supposed to provide up to $20,000 in debt cancellation to Pell Grant recipients who have loans that are held by the Department of Education. Borrowers can get this relief if their income is less than $125,000 for an individual or $250,000 for married couples.

Many people have looked at this and said, “Hey, wait a minute. I paid off my loans. I didn’t get any reimbursement. That isn’t fair.”

One group saddled with massive debt are people who are still carrying their medical school loans, who often still have huge amounts of debt, and either because of the income limits or because they don’t qualify because this debt was accrued long in the past, they’re saying, “What about me? Don’t you want to give any relief to me?”

This is a topic near and dear to my heart because I happen to be at a medical school, NYU, that has decided for the two medical schools it runs – our main campus, NYU in Manhattan and NYU Langone out on Long Island – that we’re going to go tuition free. We’ve done it for a couple of years.

We did it because I think all the administrators and faculty understood the tremendous burden that debt poses on people who both carry forward their undergraduate debt and then have medical school debt. This really leads to very difficult situations – which we have great empathy for – about what specialty you’re going to go into, whether you have to moonlight, and how you’re going to manage a huge burden of debt.

Many people don’t have sympathy out in the public. They say doctors make a large amount of money and they live a nice lifestyle, so we’re not going to relieve their debt. The reality is that, whoever you are, short of Bill Gates or Elon Musk, having hundreds of thousands of dollars of debt is no easy task to live with and to work off.

Still, when we created free tuition at NYU for our medical school, there were many people who paid high tuition fees in the past. Some of them said to us, “What about me?” We decided not to try to do anything retrospectively. The plan was to build up enough money so that we could handle no-cost tuition going forward. We didn’t really have it in our pocketbook to help people who’d already paid their debts or were saddled with NYU debt. Is it fair? No, it’s probably not fair, but it’s an improvement.

That’s what I want people to think about who are saying, “What about my medical school debt? What about my undergraduate plus medical school debt?” I think we should be grateful when efforts are being made to reduce very burdensome student loans that people have. It’s good to give that benefit and move it forward.

Does that mean no one should get anything unless everyone with any kind of debt from school is covered? I don’t think so. I don’t think that’s fair either.

It is possible that we could continue to agitate politically and say, let’s go after some of the health care debt. Let’s go after some of the things that are still driving people to have to work more than they would or to choose specialties that they really don’t want to be in because they have to make up that debt.

It doesn’t mean the last word has been said about the politics of debt relief or, for that matter, the price of going to medical school in the first place and trying to see whether that can be driven down.

I don’t think it’s right to say, “If I can’t benefit, given the huge burden that I’m carrying, then I’m not going to try to give relief to others.” I think we’re relieving debt to the extent that we can do it. The nation can afford it. Going forward is a good thing. It’s wrong to create those gigantic debts in the first place.

What are we going to do about the past? We may decide that we need some sort of forgiveness or reparations for loans that were built up for others going backwards. I wouldn’t hold hostage the future and our children to what was probably a very poor, unethical practice about saddling doctors and others in the past with huge debt.

I’m Art Caplan at the division of medical ethics at New York University Grossman School of Medicine. Thank you for watching.

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I run the division of medical ethics at New York University Grossman School of Medicine.

Many of you know that President Biden created a loan forgiveness program, forgiving up to $10,000 against federal student loans, including graduate and undergraduate education. The Department of Education is supposed to provide up to $20,000 in debt cancellation to Pell Grant recipients who have loans that are held by the Department of Education. Borrowers can get this relief if their income is less than $125,000 for an individual or $250,000 for married couples.

Many people have looked at this and said, “Hey, wait a minute. I paid off my loans. I didn’t get any reimbursement. That isn’t fair.”

One group saddled with massive debt are people who are still carrying their medical school loans, who often still have huge amounts of debt, and either because of the income limits or because they don’t qualify because this debt was accrued long in the past, they’re saying, “What about me? Don’t you want to give any relief to me?”

This is a topic near and dear to my heart because I happen to be at a medical school, NYU, that has decided for the two medical schools it runs – our main campus, NYU in Manhattan and NYU Langone out on Long Island – that we’re going to go tuition free. We’ve done it for a couple of years.

We did it because I think all the administrators and faculty understood the tremendous burden that debt poses on people who both carry forward their undergraduate debt and then have medical school debt. This really leads to very difficult situations – which we have great empathy for – about what specialty you’re going to go into, whether you have to moonlight, and how you’re going to manage a huge burden of debt.

Many people don’t have sympathy out in the public. They say doctors make a large amount of money and they live a nice lifestyle, so we’re not going to relieve their debt. The reality is that, whoever you are, short of Bill Gates or Elon Musk, having hundreds of thousands of dollars of debt is no easy task to live with and to work off.

Still, when we created free tuition at NYU for our medical school, there were many people who paid high tuition fees in the past. Some of them said to us, “What about me?” We decided not to try to do anything retrospectively. The plan was to build up enough money so that we could handle no-cost tuition going forward. We didn’t really have it in our pocketbook to help people who’d already paid their debts or were saddled with NYU debt. Is it fair? No, it’s probably not fair, but it’s an improvement.

That’s what I want people to think about who are saying, “What about my medical school debt? What about my undergraduate plus medical school debt?” I think we should be grateful when efforts are being made to reduce very burdensome student loans that people have. It’s good to give that benefit and move it forward.

Does that mean no one should get anything unless everyone with any kind of debt from school is covered? I don’t think so. I don’t think that’s fair either.

It is possible that we could continue to agitate politically and say, let’s go after some of the health care debt. Let’s go after some of the things that are still driving people to have to work more than they would or to choose specialties that they really don’t want to be in because they have to make up that debt.

It doesn’t mean the last word has been said about the politics of debt relief or, for that matter, the price of going to medical school in the first place and trying to see whether that can be driven down.

I don’t think it’s right to say, “If I can’t benefit, given the huge burden that I’m carrying, then I’m not going to try to give relief to others.” I think we’re relieving debt to the extent that we can do it. The nation can afford it. Going forward is a good thing. It’s wrong to create those gigantic debts in the first place.

What are we going to do about the past? We may decide that we need some sort of forgiveness or reparations for loans that were built up for others going backwards. I wouldn’t hold hostage the future and our children to what was probably a very poor, unethical practice about saddling doctors and others in the past with huge debt.

I’m Art Caplan at the division of medical ethics at New York University Grossman School of Medicine. Thank you for watching.

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

This transcript has been edited for clarity.

Hi. I’m Art Caplan. I run the division of medical ethics at New York University Grossman School of Medicine.

Many of you know that President Biden created a loan forgiveness program, forgiving up to $10,000 against federal student loans, including graduate and undergraduate education. The Department of Education is supposed to provide up to $20,000 in debt cancellation to Pell Grant recipients who have loans that are held by the Department of Education. Borrowers can get this relief if their income is less than $125,000 for an individual or $250,000 for married couples.

Many people have looked at this and said, “Hey, wait a minute. I paid off my loans. I didn’t get any reimbursement. That isn’t fair.”

One group saddled with massive debt are people who are still carrying their medical school loans, who often still have huge amounts of debt, and either because of the income limits or because they don’t qualify because this debt was accrued long in the past, they’re saying, “What about me? Don’t you want to give any relief to me?”

This is a topic near and dear to my heart because I happen to be at a medical school, NYU, that has decided for the two medical schools it runs – our main campus, NYU in Manhattan and NYU Langone out on Long Island – that we’re going to go tuition free. We’ve done it for a couple of years.

We did it because I think all the administrators and faculty understood the tremendous burden that debt poses on people who both carry forward their undergraduate debt and then have medical school debt. This really leads to very difficult situations – which we have great empathy for – about what specialty you’re going to go into, whether you have to moonlight, and how you’re going to manage a huge burden of debt.

Many people don’t have sympathy out in the public. They say doctors make a large amount of money and they live a nice lifestyle, so we’re not going to relieve their debt. The reality is that, whoever you are, short of Bill Gates or Elon Musk, having hundreds of thousands of dollars of debt is no easy task to live with and to work off.

Still, when we created free tuition at NYU for our medical school, there were many people who paid high tuition fees in the past. Some of them said to us, “What about me?” We decided not to try to do anything retrospectively. The plan was to build up enough money so that we could handle no-cost tuition going forward. We didn’t really have it in our pocketbook to help people who’d already paid their debts or were saddled with NYU debt. Is it fair? No, it’s probably not fair, but it’s an improvement.

That’s what I want people to think about who are saying, “What about my medical school debt? What about my undergraduate plus medical school debt?” I think we should be grateful when efforts are being made to reduce very burdensome student loans that people have. It’s good to give that benefit and move it forward.

Does that mean no one should get anything unless everyone with any kind of debt from school is covered? I don’t think so. I don’t think that’s fair either.

It is possible that we could continue to agitate politically and say, let’s go after some of the health care debt. Let’s go after some of the things that are still driving people to have to work more than they would or to choose specialties that they really don’t want to be in because they have to make up that debt.

It doesn’t mean the last word has been said about the politics of debt relief or, for that matter, the price of going to medical school in the first place and trying to see whether that can be driven down.

I don’t think it’s right to say, “If I can’t benefit, given the huge burden that I’m carrying, then I’m not going to try to give relief to others.” I think we’re relieving debt to the extent that we can do it. The nation can afford it. Going forward is a good thing. It’s wrong to create those gigantic debts in the first place.

What are we going to do about the past? We may decide that we need some sort of forgiveness or reparations for loans that were built up for others going backwards. I wouldn’t hold hostage the future and our children to what was probably a very poor, unethical practice about saddling doctors and others in the past with huge debt.

I’m Art Caplan at the division of medical ethics at New York University Grossman School of Medicine. Thank you for watching.

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

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

This article was originally published Oct. 8 on Medscape Editor-In-Chief Eric Topol’s “Ground Truths” column on Substack. 

A recent piece in The Economist about masks, and how at least half of the people in Japan are planning to continue to use masks indefinitely (where there was never a mandate), prompts a deeper look into what has been the secret of Japan’s extraordinary success in the pandemic. Over time it has the least cumulative deaths per capita of any major country in the world. That’s without a zero-Covid policy or any national lockdowns, which is why I have not included China as a comparator.

Before we get into that data, let’s take a look at the age pyramids for Japan and the United States. The No. 1 risk factor for death from COVID-19 is advanced age, and you can see that in Japan about 25% of the population is age 65 and older, whereas in the United States that proportion is substantially reduced at 15%. Sure there are differences in comorbidities such as obesity and diabetes, but there is also the trade-off of a much higher population density in Japan.

Besides masks, which were distributed early on by the government to the population in Japan, there was the “Avoid the 3Cs” cluster-busting strategy, widely disseminated in the spring of 2020, leveraging Pareto’s 80-20 principle, long before there were any vaccines available. For a good portion of the pandemic, the Ministry of Foreign Affairs of Japan maintained a strict policy for border control, which while hard to quantify, may certainly have contributed to its success.

Besides these factors, once vaccines became available, Japan got the population with the primary series to 83% rapidly, even after getting a late start by many months compared with the United States, which has peaked at 68%. That’s a big gap.

But that gap got much worse when it came to boosters. Ninety-five percent of Japanese eligible compared with 40.8% of Americans have had a booster shot. Of note, that 95% in Japan pertains to the whole population. In the United States the percentage of people age 65 and older who have had two boosters is currently only 42%. I’ve previously reviewed the important lifesaving impact of two boosters among people age 65 and older from five independent studies during Omicron waves throughout the world.

Now let’s turn to cumulative fatalities in the two countries. There’s a huge, nearly ninefold difference, per capita. Using today’s Covid-19 Dashboard, there are cumulatively 45,533 deaths in Japan and 1,062,560 American deaths. That translates to 1 in 2,758 people in Japan compared with 1 in 315 Americans dying of COVID.

And if we look at excess mortality instead of confirmed COVID deaths, that enormous gap doesn’t change.

Obviously it would be good to have data for other COVID outcomes, such as hospitalizations, ICUs, and Long COVID, but they are not accessible.

Comparing Japan, the country that has fared the best, with the United States, one of the worst pandemic outcome results, leaves us with a sense that Prof Ian MacKay’s “Swiss cheese model” is the best explanation. It’s not just one thing. Masks, consistent evidence-based communication (3Cs) with attention to ventilation and air quality, and the outstanding uptake of vaccines and boosters all contributed to Japan’s success.

There is another factor to add to that model – Paxlovid. Its benefit of reducing hospitalizations and deaths for people over age 65 is unquestionable.

That’s why I had previously modified the Swiss cheese model to add Paxlovid.

But in the United States, where 15% of the population is 65 and older, they account for over 75% of the daily death toll, still in the range of 400 per day. Here, with a very high proportion of people age 65 and older left vulnerable without boosters, or primary vaccines, Paxlovid is only being given to less than 25% of the eligible (age 50+), and less people age 80 and older are getting Paxlovid than those age 45. The reasons that doctors are not prescribing it – worried about interactions for a 5-day course and rebound – are not substantiated.

Bottom line: In the United States we are not protecting our population anywhere near as well as Japan, as grossly evident by the fatalities among people at the highest risk. There needs to be far better uptake of boosters and use of Paxlovid in the age 65+ group, but the need for amped up protection is not at all restricted to this age subgroup. Across all age groups age 18 and over there is an 81% reduction of hospitalizations with two boosters with the most updated CDC data available, through the Omicron BA.5 wave.

No less the previous data through May 2022 showing protection from death across all ages with two boosters

And please don’t forget that around the world, over 20 million lives were saved, just in 2021, the first year of vaccines.

We can learn so much from a model country like Japan. Yes, we need nasal and variant-proof vaccines to effectively deal with the new variants that are already getting legs in places like XBB in Singapore and ones not on the radar yet. But right now we’ve got to do far better for people getting boosters and, when a person age 65 or older gets COVID, Paxlovid. Take a look at the Chris Hayes video segment when he pleaded for Americans to get a booster shot. Every day that vaccine waning of the U.S. population exceeds the small percentage of people who get a booster, our vulnerability increases. If we don’t get that on track, it’s likely going to be a rough winter ahead.

Dr. Topol is director of the Scripps Translational Science Institute in La Jolla, Calif. He has received research grants from the National Institutes of Health and reported conflicts of interest involving Dexcom, Illumina, Molecular Stethoscope, Quest Diagnostics, and Blue Cross Blue Shield Association. A version of this article appeared on Medscape.com.

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Mitchel L. Zoler/MDedge News

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Mitchel L. Zoler/MDedge News

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.

STOCKHOLM – New insights into the benefits of treatment with the “twincretin” tirzepatide for people with overweight or obesity – with or without diabetes – come from new findings reported at the annual meeting of the European Association for the Study of Diabetes.

Additional results from the SURMOUNT-1 trial, which matched tirzepatide against placebo in people with overweight or obesity, provide further details on the favorable changes produced by 72 weeks of tirzepatide treatment on outcomes that included fat and lean mass, insulin sensitivity, and patient-reported outcomes related to functional health and well being, reported Ania M. Jastreboff, MD, PhD.

Mitchel L. Zoler/MDedge News

And results from a meta-analysis of six trials that compared tirzepatide (Mounjaro) against several different comparators in patients with type 2 diabetes further confirm the drug’s ability to reliably produce positive changes in blood lipids, especially by significantly lowering levels of triglycerides, LDL cholesterol, and very LDL (VLDL) cholesterol, said Thomas Karagiannis, MD, PhD, in a separate report at the meeting.

Tirzepatide works as an agonist on receptors for both the glucagonlike peptide–1 (GLP-1), and for the glucose-dependent insulinotropic polypeptide, and received Food and Drug Administration approval for treating people with type 2 diabetes in May 2022. On the basis of results from SURMOUNT-1, the FDA on Oct. 6 granted tirzepatide fast-track designation for a proposed labeling of the agent for treating people with overweight or obesity. This FDA decision will likely remain pending at least until results from a second trial in people with overweight or obesity but without diabetes, SURMOUNT-2, become available in 2023.

SURMOUNT-1 randomized 2,539 people with obesity or overweight and at least one weight-related complication to a weekly injection of tirzepatide or placebo for 72 weeks. The study’s primary efficacy endpoints were the average reduction in weight from baseline, and the percentage of people in each treatment arm achieving weight loss of at least 5% from baseline.

For both endpoints, the outcomes with tirzepatide significantly surpassed placebo effects. Average weight loss ranged from 15%-21% from baseline, depending on dose, compared with 3% on placebo. The rate of participants with at least a 5% weight loss ranged from 85% to 91%, compared with 35% with placebo, as reported in July 2022 in the New England Journal of Medicine.

Cutting fat mass, boosting lean mass

New results from the trial reported by Dr. Jastreboff included a cut in fat mass from 46.2% of total body mass at baseline to 38.5% after 72 weeks, compared with a change from 46.8% at baseline to 44.7% after 72 weeks in the placebo group. Concurrently, lean mass increased with tirzepatide treatment from 51.0% at baseline to 58.1% after 72 weeks.

Participants who received tirzepatide, compared with those who received placebo, had “proportionately greater decrease in fat mass and proportionately greater increase in lean mass” compared with those who received placebo, said Dr. Jastreboff, an endocrinologist and obesity medicine specialist with Yale Medicine in New Haven, Conn. “I was impressed by the amount of visceral fat lost.”

These effects translated into a significant reduction in fat mass-to-lean mass ratio among the people treated with tirzepatide, with the greatest reduction in those who lost at least 15% of their starting weight. In that subgroup the fat-to-lean mass ratio dropped from 0.94 at baseline to 0.64 after 72 weeks of treatment, she said.
 

Focus on diet quality

People treated with tirzepatide “eat so little food that we need to improve the quality of what they eat to protect their muscle,” commented Carel le Roux, MBChB, PhD, a professor in the Diabetes Complications Research Centre of University College Dublin. “You no longer need a dietitian to help people lose weight, because the drug does that. You need dietitians to look after the nutritional health of patients while they lose weight,” Dr. le Roux said in a separate session at the meeting.

Mitchel L. Zoler/MDedge News

Additional tests showed that blood glucose and insulin levels were all significantly lower among trial participants on all three doses of tirzepatide compared with those on placebo, and the tirzepatide-treated subjects also had significant, roughly twofold elevations in their insulin sensitivity measured by the Matsuda Index.

The impact of tirzepatide on glucose and insulin levels and on insulin sensitivity was similar regardless of whether study participants had normoglycemia or prediabetes at entry. By design, no study participants had diabetes.

The trial assessed patient-reported quality-of-life outcomes using the 36-Item Short Form Survey (SF-36). Participants had significant increases in all eight domains within the SF-36 at all three tirzepatide doses, compared with placebo, at 72 weeks, Dr. Jastreboff reported. Improvements in the physical function domain increased most notably among study participants on tirzepatide who had functional limitations at baseline. Heart rate rose among participants who received either of the two highest tirzepatide doses by 2.3-2.5 beats/min, comparable with the effect of other injected incretin-based treatments.

Lipids improve in those with type 2 diabetes

Tirzepatide treatment also results in a “secondary effect” of improving levels of several lipids in people with type 2 diabetes, according to a meta-analysis of findings from six randomized trials. The meta-analysis collectively involved 4,502 participants treated for numerous weeks with one of three doses of tirzepatide and 2,144 people in comparator groups, reported Dr. Karagiannis, a diabetes researcher at Aristotle University of Thessaloniki (Greece).

Among the significant lipid changes linked with tirzepatide treatment, compared with placebo, were an average 13 mg/dL decrease in LDL cholesterol, an average 6 mg/dL decrease in VLDL cholesterol, and an average 50 mg/dL decrease in triglycerides. In comparison to a GLP-1 receptor agonist, an average 25 mg/dL decrease in triglycerides and an average 4 mg/dL reduction in VLDL cholesterol were seen. And trials comparing tirzepatide with basal insulin saw average reductions of 7% in LDL cholesterol, 15% in VLDL cholesterol, 15% in triglycerides, and an 8% increase in HDL cholesterol.

Dr. Karagiannis highlighted that the clinical impact of these effects is unclear, although he noted that the average reduction in LDL cholesterol relative to placebo is of a magnitude that could have a modest effect on long-term outcomes.

These lipid effects of tirzepatide “should be considered alongside” tirzepatide’s “key metabolic effects” on weight and hemoglobin A1c as well as the drug’s safety, concluded Dr. Karagiannis.

The tirzepatide trials were all funded by Eli Lilly, which markets tirzepatide (Mounjaro). Dr. Jastreboff has been an adviser and consultant to Eli Lilly, as well as to Intellihealth, Novo Nordisk, Pfizer, Rhythm Scholars, Roche, and Weight Watchers, and she has received research funding from Eli Lilly and Novo Nordisk. Dr. Karagiannis had no disclosures. Dr. le Roux has had financial relationships with Eli Lilly, as well as with Boehringer Ingelheim, Consilient Health, Covidion, Fractyl, GL Dynamics, Herbalife, Johnson & Johnson, Keyron, and Novo Nordisk.

I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon’s knife or the chemist’s drug.

Upon finishing medical school, many of us recited this passage from a modernized version of the Hippocratic Oath. Though there has been controversy regarding the current relevancy of this oath, it can still serve as a reminder of the promises we made on behalf of our patients: To treat them ethically, with empathy and respect, and without pretension. Though I hadn’t thought about the Hippocratic Oath in ages, it came to mind recently after I read an article about weight trends in adults during the COVID pandemic.

No surprise – we gained weight during the initial surge at a rate of roughly a pound and a half per month following the initial shelter-in-place period. For some of us, that trend in weight gain worsened as the pandemic persisted. A survey conducted in February 2021 suggested that over 40% of adults who experienced undesired weight changes since the start of the pandemic gained an average of 29 pounds (significantly more than the typical gain of 15 pounds, often referred to as the “Quarantine 15” or “COVID-15”).

Updated data, obtained via a review of electronic health records for over 15 million patients, shows that 39% of patients gained weight during the pandemic (10% of them gained more than 12.5 pounds, while 2% gained over 27.5 pounds). Though these recent numbers may be lower than previously reported, they still aren’t reassuring. As our bodies have changed, so has the concern for worsening weight stigma (bias against individuals because of their body size).

Research has already confirmed that sizeism has a negative impact on both a patient’s physical health and psychological well-being, and as medical providers, we’re part of the problem. We cause distress in our patients through disrespectful treatment and medical fat shaming, which can lead to cycles of disordered eating, reduced physical activity, and more weight gain. We discriminate based on weight, causing our patients to delay health care visits and other provider interactions, resulting in increased risks for morbidity and even mortality. We make assumptions that a patient’s presenting complaints are due to weight rather than other causes, resulting in missed diagnoses. And we recommend different treatments for obese patients with the same condition as nonobese patients simply because of their weight.

One study has suggested that over 40% of adults in the United States have suffered from weight stigma, and physicians and coworkers are listed as some of the most common sources. Another study suggests that nearly 70% of overweight or obese patients report feeling stigmatized by physicians, whether through expressed biases or purposeful avoidance (patients have previously reported that their providers addressed weight loss in fewer than 20% of their examinations).

As health care providers, we need to do better. We should all be willing to consider our own biases about body size, and there are self-assessments to help with this, including the Implicit Associations Test: Weight Bias. By becoming more self-aware, hopefully we can change the doctor-patient conversation about weight management.

Studies have shown that meaningful conversations with physicians can have a significant impact on patients’ attempts to change behaviors related to weight. Yet, many medical providers are not trained in how to counsel patients on nutrition, weight loss, and physical activity (if we bring it up at all). We need to better educate ourselves about weight science and treatments.

In the meantime, we can work on how we interact with our patients:

• Make sure that your practice space is accommodating and nondiscriminatory, with appropriately sized furniture in the waiting and exam rooms, large blood pressure cuffs and gowns, and size-inclusive reading materials.
• Ensure that your workplace has an antiharassment policy that includes sizeism.
• Be an ally and speak up against weight discrimination.
• Educate your office staff about weight stigma and ensure that they avoid commenting on the weight or body size of others (being recognized only for losing weight isn’t a compliment, and sharing “fat jokes” isn’t funny).
• Remember that a person’s body size tells you nothing about that person’s health behaviors. Stop assuming that larger body sizes are related to laziness, overeating, or a lack of motivation.
• Ask your overweight or obese patients if they are willing to talk about their weight before jumping into the topic.
• Practice (patients are more likely to report changing their exercise routine and attempting to lose weight with these techniques).
• Be mindful of your word choices; for example, it can be more helpful to focus on comorbidities (such as high blood pressure or prediabetes) rather than body weight, nutrition rather than dieting, and physical activity rather than specific exercises.

Regardless of how you feel about reciting the Hippocratic Oath, our patients, no matter their body size, deserve to be treated with respect and dignity, as others have said in more eloquent ways than I. Let’s stop playing the fat shame game and help fight weight bias in medicine.

Dr. Devlin is president, Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She reported no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon’s knife or the chemist’s drug.

Upon finishing medical school, many of us recited this passage from a modernized version of the Hippocratic Oath. Though there has been controversy regarding the current relevancy of this oath, it can still serve as a reminder of the promises we made on behalf of our patients: To treat them ethically, with empathy and respect, and without pretension. Though I hadn’t thought about the Hippocratic Oath in ages, it came to mind recently after I read an article about weight trends in adults during the COVID pandemic.

No surprise – we gained weight during the initial surge at a rate of roughly a pound and a half per month following the initial shelter-in-place period. For some of us, that trend in weight gain worsened as the pandemic persisted. A survey conducted in February 2021 suggested that over 40% of adults who experienced undesired weight changes since the start of the pandemic gained an average of 29 pounds (significantly more than the typical gain of 15 pounds, often referred to as the “Quarantine 15” or “COVID-15”).

Updated data, obtained via a review of electronic health records for over 15 million patients, shows that 39% of patients gained weight during the pandemic (10% of them gained more than 12.5 pounds, while 2% gained over 27.5 pounds). Though these recent numbers may be lower than previously reported, they still aren’t reassuring. As our bodies have changed, so has the concern for worsening weight stigma (bias against individuals because of their body size).

Research has already confirmed that sizeism has a negative impact on both a patient’s physical health and psychological well-being, and as medical providers, we’re part of the problem. We cause distress in our patients through disrespectful treatment and medical fat shaming, which can lead to cycles of disordered eating, reduced physical activity, and more weight gain. We discriminate based on weight, causing our patients to delay health care visits and other provider interactions, resulting in increased risks for morbidity and even mortality. We make assumptions that a patient’s presenting complaints are due to weight rather than other causes, resulting in missed diagnoses. And we recommend different treatments for obese patients with the same condition as nonobese patients simply because of their weight.

One study has suggested that over 40% of adults in the United States have suffered from weight stigma, and physicians and coworkers are listed as some of the most common sources. Another study suggests that nearly 70% of overweight or obese patients report feeling stigmatized by physicians, whether through expressed biases or purposeful avoidance (patients have previously reported that their providers addressed weight loss in fewer than 20% of their examinations).

As health care providers, we need to do better. We should all be willing to consider our own biases about body size, and there are self-assessments to help with this, including the Implicit Associations Test: Weight Bias. By becoming more self-aware, hopefully we can change the doctor-patient conversation about weight management.

Studies have shown that meaningful conversations with physicians can have a significant impact on patients’ attempts to change behaviors related to weight. Yet, many medical providers are not trained in how to counsel patients on nutrition, weight loss, and physical activity (if we bring it up at all). We need to better educate ourselves about weight science and treatments.

In the meantime, we can work on how we interact with our patients:

• Make sure that your practice space is accommodating and nondiscriminatory, with appropriately sized furniture in the waiting and exam rooms, large blood pressure cuffs and gowns, and size-inclusive reading materials.
• Ensure that your workplace has an antiharassment policy that includes sizeism.
• Be an ally and speak up against weight discrimination.
• Educate your office staff about weight stigma and ensure that they avoid commenting on the weight or body size of others (being recognized only for losing weight isn’t a compliment, and sharing “fat jokes” isn’t funny).
• Remember that a person’s body size tells you nothing about that person’s health behaviors. Stop assuming that larger body sizes are related to laziness, overeating, or a lack of motivation.
• Ask your overweight or obese patients if they are willing to talk about their weight before jumping into the topic.
• Practice (patients are more likely to report changing their exercise routine and attempting to lose weight with these techniques).
• Be mindful of your word choices; for example, it can be more helpful to focus on comorbidities (such as high blood pressure or prediabetes) rather than body weight, nutrition rather than dieting, and physical activity rather than specific exercises.

Regardless of how you feel about reciting the Hippocratic Oath, our patients, no matter their body size, deserve to be treated with respect and dignity, as others have said in more eloquent ways than I. Let’s stop playing the fat shame game and help fight weight bias in medicine.

Dr. Devlin is president, Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She reported no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon’s knife or the chemist’s drug.

Upon finishing medical school, many of us recited this passage from a modernized version of the Hippocratic Oath. Though there has been controversy regarding the current relevancy of this oath, it can still serve as a reminder of the promises we made on behalf of our patients: To treat them ethically, with empathy and respect, and without pretension. Though I hadn’t thought about the Hippocratic Oath in ages, it came to mind recently after I read an article about weight trends in adults during the COVID pandemic.

No surprise – we gained weight during the initial surge at a rate of roughly a pound and a half per month following the initial shelter-in-place period. For some of us, that trend in weight gain worsened as the pandemic persisted. A survey conducted in February 2021 suggested that over 40% of adults who experienced undesired weight changes since the start of the pandemic gained an average of 29 pounds (significantly more than the typical gain of 15 pounds, often referred to as the “Quarantine 15” or “COVID-15”).

Updated data, obtained via a review of electronic health records for over 15 million patients, shows that 39% of patients gained weight during the pandemic (10% of them gained more than 12.5 pounds, while 2% gained over 27.5 pounds). Though these recent numbers may be lower than previously reported, they still aren’t reassuring. As our bodies have changed, so has the concern for worsening weight stigma (bias against individuals because of their body size).

Research has already confirmed that sizeism has a negative impact on both a patient’s physical health and psychological well-being, and as medical providers, we’re part of the problem. We cause distress in our patients through disrespectful treatment and medical fat shaming, which can lead to cycles of disordered eating, reduced physical activity, and more weight gain. We discriminate based on weight, causing our patients to delay health care visits and other provider interactions, resulting in increased risks for morbidity and even mortality. We make assumptions that a patient’s presenting complaints are due to weight rather than other causes, resulting in missed diagnoses. And we recommend different treatments for obese patients with the same condition as nonobese patients simply because of their weight.

One study has suggested that over 40% of adults in the United States have suffered from weight stigma, and physicians and coworkers are listed as some of the most common sources. Another study suggests that nearly 70% of overweight or obese patients report feeling stigmatized by physicians, whether through expressed biases or purposeful avoidance (patients have previously reported that their providers addressed weight loss in fewer than 20% of their examinations).

As health care providers, we need to do better. We should all be willing to consider our own biases about body size, and there are self-assessments to help with this, including the Implicit Associations Test: Weight Bias. By becoming more self-aware, hopefully we can change the doctor-patient conversation about weight management.

Studies have shown that meaningful conversations with physicians can have a significant impact on patients’ attempts to change behaviors related to weight. Yet, many medical providers are not trained in how to counsel patients on nutrition, weight loss, and physical activity (if we bring it up at all). We need to better educate ourselves about weight science and treatments.

In the meantime, we can work on how we interact with our patients:

• Make sure that your practice space is accommodating and nondiscriminatory, with appropriately sized furniture in the waiting and exam rooms, large blood pressure cuffs and gowns, and size-inclusive reading materials.
• Ensure that your workplace has an antiharassment policy that includes sizeism.
• Be an ally and speak up against weight discrimination.
• Educate your office staff about weight stigma and ensure that they avoid commenting on the weight or body size of others (being recognized only for losing weight isn’t a compliment, and sharing “fat jokes” isn’t funny).
• Remember that a person’s body size tells you nothing about that person’s health behaviors. Stop assuming that larger body sizes are related to laziness, overeating, or a lack of motivation.
• Ask your overweight or obese patients if they are willing to talk about their weight before jumping into the topic.
• Practice (patients are more likely to report changing their exercise routine and attempting to lose weight with these techniques).
• Be mindful of your word choices; for example, it can be more helpful to focus on comorbidities (such as high blood pressure or prediabetes) rather than body weight, nutrition rather than dieting, and physical activity rather than specific exercises.

Regardless of how you feel about reciting the Hippocratic Oath, our patients, no matter their body size, deserve to be treated with respect and dignity, as others have said in more eloquent ways than I. Let’s stop playing the fat shame game and help fight weight bias in medicine.

Dr. Devlin is president, Locum Infectious Disease Services, and an independent contractor for Weatherby Healthcare. She reported no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

About 1 in 20 people with long COVID continue to live with symptoms at 18 months, and another 42% reported only some improvement in their health and wellbeing in the same time frame, a large study out of Scotland found.

Multiple studies are evaluating people with long COVID in the hopes of figuring out why some people experience debilitating symptoms long after their primary infection ends and others either do not or recover more quickly. 

This current study is notable for its large size – 96,238 people. Researchers checked in with participants at 6, 12, and 18 months, and included a group of people never infected with the coronavirus to help investigators make a stronger case.

“A lot of the symptoms of long COVID are nonspecific and therefore can occur in people never infected,” says senior study author Jill P. Pell, MD, head of the School of Health and Wellbeing at the University of Glasgow in Scotland. 
 

Ruling out coincidence

This study shows that people experienced a wide range of symptoms after becoming infected with COVID-19 at a significantly higher rate than those who were never infected, “thereby confirming that they were genuinely associated with COVID and not merely a coincidence,” she said. 

Among 21,525 people who had COVID-19 and had symptoms, tiredness, headache and muscle aches or muscle weakness were the most common ongoing symptoms. 

Loss of smell was almost nine times more likely in this group compared to the never-infected group in one analysis where researchers controlled for other possible factors. The risk for loss of taste was almost six times greater, followed by risk of breathlessness at three times higher. 

Long COVID risk was highest after a severe original infection and among older people, women, Black, and South Asian populations, people with socioeconomic disadvantages, and those with more than one underlying health condition.

Adding up the 6% with no recovery after 18 months and 42% with partial recovery means that between 6 and 18 months following symptomatic coronavirus infection, almost half of those infected still experience persistent symptoms.
 

Vaccination validated

On the plus side, people vaccinated against COVID-19 before getting infected had a lower risk for some persistent symptoms. In addition, Dr. Pell and colleagues found no evidence that people who experienced asymptomatic infection were likely to experience long COVID symptoms or challenges with activities of daily living. 

The findings of the Long-COVID in Scotland Study (Long-CISS) were published in the journal Nature Communications.
 

‘More long COVID than ever before’

“Unfortunately, these long COVID symptoms are not getting better as the cases of COVID get milder,” said Thomas Gut, DO, medical director for the post-COVID recovery program at Staten Island (N.Y.) University Hospital. “Quite the opposite – this infection has become so common in a community because it’s so mild and spreading so rapidly that we’re seeing more long COVID symptoms than ever before.” 

Although most patients he sees with long COVID resolve their symptoms within 3-6 months, “We do see some patients who require short-term disability because their symptoms continue past 6 months and out to 2 years,” said Dr. Gut, a hospitalist at Staten Island University Hospital, a member hospital of Northwell Health.

Patients with fatigue and neurocognitive symptoms “have a very tough time going back to work. Short-term disability gives them the time and finances to pursue specialty care with cardiology, pulmonary, and neurocognitive testing,” he said.
 

Support the whole person

The burden of living with long COVID goes beyond the persistent symptoms. “Long COVID can have wide-ranging impacts – not only on health but also quality of life and activities of daily living [including] work, mobility, self-care and more,” Dr. Pell said. “So, people with long COVID need support relevant to their individual needs and this may extend beyond the health care sector, for example including social services, school or workplace.”

Still,  Lisa Penziner, RN, founder of the COVID Long Haulers Support Group in Westchester and Long Island, N.Y., said while people with the most severe cases of COVID-19 tended to have the worst long COVID symptoms, they’re not the only ones. 

“We saw many post-COVID members who had mild cases and their long-haul symptoms were worse weeks later than the virus itself,” said Md. Penziner. 

She estimates that 80%-90% of her support group members recover within 6 months. “However, there are others who were experiencing symptoms for much longer.”

Respiratory treatment, physical therapy, and other follow-up doctor visits are common after 6 months, for example. 

“Additionally, there is a mental health component to recovery as well, meaning that the patient must learn to live while experiencing lingering, long-haul COVID symptoms in work and daily life,” said Ms. Penziner, director of special projects at North Westchester Restorative Therapy & Nursing. 

In addition to ongoing medical care, people with long COVID need understanding, she said.

“While long-haul symptoms do not happen to everyone, it is proven that many do experience long-haul symptoms, and the support of the community in understanding is important.”
 

Limitations of the study

Dr. Pell and colleagues noted some strengths and weaknesses to their study. For example, “as a general population study, our findings provide a better indication of the overall risk and burden of long COVID than hospitalized cohorts,” they noted. 

Also, the Scottish population is 96% White, so other long COVID studies with more diverse participants are warranted. 

Another potential weakness is the response rate of 16% among those invited to participate in the study, which Dr. Pell and colleagues addressed: “Our cohort included a large sample (33,281) of people previously infected and the response rate of 16% overall and 20% among people who had symptomatic infection was consistent with previous studies that have used SMS text invitations as the sole method of recruitment.”

“We tell patients this should last 3-6 months, but some patients have longer recovery periods,” Dr. Gut said. “We’re here for them. We have a lot of services available to help get them through the recovery process, and we have a lot of options to help support them.”

“What we found most helpful is when there is peer-to-peer support, reaffirming to the member that they are not alone in the long-haul battle, which has been a major benefit of the support group,” Ms. Penziner said.

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

About 1 in 20 people with long COVID continue to live with symptoms at 18 months, and another 42% reported only some improvement in their health and wellbeing in the same time frame, a large study out of Scotland found.

Multiple studies are evaluating people with long COVID in the hopes of figuring out why some people experience debilitating symptoms long after their primary infection ends and others either do not or recover more quickly. 

This current study is notable for its large size – 96,238 people. Researchers checked in with participants at 6, 12, and 18 months, and included a group of people never infected with the coronavirus to help investigators make a stronger case.

“A lot of the symptoms of long COVID are nonspecific and therefore can occur in people never infected,” says senior study author Jill P. Pell, MD, head of the School of Health and Wellbeing at the University of Glasgow in Scotland. 
 

Ruling out coincidence

This study shows that people experienced a wide range of symptoms after becoming infected with COVID-19 at a significantly higher rate than those who were never infected, “thereby confirming that they were genuinely associated with COVID and not merely a coincidence,” she said. 

Among 21,525 people who had COVID-19 and had symptoms, tiredness, headache and muscle aches or muscle weakness were the most common ongoing symptoms. 

Loss of smell was almost nine times more likely in this group compared to the never-infected group in one analysis where researchers controlled for other possible factors. The risk for loss of taste was almost six times greater, followed by risk of breathlessness at three times higher. 

Long COVID risk was highest after a severe original infection and among older people, women, Black, and South Asian populations, people with socioeconomic disadvantages, and those with more than one underlying health condition.

Adding up the 6% with no recovery after 18 months and 42% with partial recovery means that between 6 and 18 months following symptomatic coronavirus infection, almost half of those infected still experience persistent symptoms.
 

Vaccination validated

On the plus side, people vaccinated against COVID-19 before getting infected had a lower risk for some persistent symptoms. In addition, Dr. Pell and colleagues found no evidence that people who experienced asymptomatic infection were likely to experience long COVID symptoms or challenges with activities of daily living. 

The findings of the Long-COVID in Scotland Study (Long-CISS) were published in the journal Nature Communications.
 

‘More long COVID than ever before’

“Unfortunately, these long COVID symptoms are not getting better as the cases of COVID get milder,” said Thomas Gut, DO, medical director for the post-COVID recovery program at Staten Island (N.Y.) University Hospital. “Quite the opposite – this infection has become so common in a community because it’s so mild and spreading so rapidly that we’re seeing more long COVID symptoms than ever before.” 

Although most patients he sees with long COVID resolve their symptoms within 3-6 months, “We do see some patients who require short-term disability because their symptoms continue past 6 months and out to 2 years,” said Dr. Gut, a hospitalist at Staten Island University Hospital, a member hospital of Northwell Health.

Patients with fatigue and neurocognitive symptoms “have a very tough time going back to work. Short-term disability gives them the time and finances to pursue specialty care with cardiology, pulmonary, and neurocognitive testing,” he said.
 

Support the whole person

The burden of living with long COVID goes beyond the persistent symptoms. “Long COVID can have wide-ranging impacts – not only on health but also quality of life and activities of daily living [including] work, mobility, self-care and more,” Dr. Pell said. “So, people with long COVID need support relevant to their individual needs and this may extend beyond the health care sector, for example including social services, school or workplace.”

Still,  Lisa Penziner, RN, founder of the COVID Long Haulers Support Group in Westchester and Long Island, N.Y., said while people with the most severe cases of COVID-19 tended to have the worst long COVID symptoms, they’re not the only ones. 

“We saw many post-COVID members who had mild cases and their long-haul symptoms were worse weeks later than the virus itself,” said Md. Penziner. 

She estimates that 80%-90% of her support group members recover within 6 months. “However, there are others who were experiencing symptoms for much longer.”

Respiratory treatment, physical therapy, and other follow-up doctor visits are common after 6 months, for example. 

“Additionally, there is a mental health component to recovery as well, meaning that the patient must learn to live while experiencing lingering, long-haul COVID symptoms in work and daily life,” said Ms. Penziner, director of special projects at North Westchester Restorative Therapy & Nursing. 

In addition to ongoing medical care, people with long COVID need understanding, she said.

“While long-haul symptoms do not happen to everyone, it is proven that many do experience long-haul symptoms, and the support of the community in understanding is important.”
 

Limitations of the study

Dr. Pell and colleagues noted some strengths and weaknesses to their study. For example, “as a general population study, our findings provide a better indication of the overall risk and burden of long COVID than hospitalized cohorts,” they noted. 

Also, the Scottish population is 96% White, so other long COVID studies with more diverse participants are warranted. 

Another potential weakness is the response rate of 16% among those invited to participate in the study, which Dr. Pell and colleagues addressed: “Our cohort included a large sample (33,281) of people previously infected and the response rate of 16% overall and 20% among people who had symptomatic infection was consistent with previous studies that have used SMS text invitations as the sole method of recruitment.”

“We tell patients this should last 3-6 months, but some patients have longer recovery periods,” Dr. Gut said. “We’re here for them. We have a lot of services available to help get them through the recovery process, and we have a lot of options to help support them.”

“What we found most helpful is when there is peer-to-peer support, reaffirming to the member that they are not alone in the long-haul battle, which has been a major benefit of the support group,” Ms. Penziner said.

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

About 1 in 20 people with long COVID continue to live with symptoms at 18 months, and another 42% reported only some improvement in their health and wellbeing in the same time frame, a large study out of Scotland found.

Multiple studies are evaluating people with long COVID in the hopes of figuring out why some people experience debilitating symptoms long after their primary infection ends and others either do not or recover more quickly. 

This current study is notable for its large size – 96,238 people. Researchers checked in with participants at 6, 12, and 18 months, and included a group of people never infected with the coronavirus to help investigators make a stronger case.

“A lot of the symptoms of long COVID are nonspecific and therefore can occur in people never infected,” says senior study author Jill P. Pell, MD, head of the School of Health and Wellbeing at the University of Glasgow in Scotland. 
 

Ruling out coincidence

This study shows that people experienced a wide range of symptoms after becoming infected with COVID-19 at a significantly higher rate than those who were never infected, “thereby confirming that they were genuinely associated with COVID and not merely a coincidence,” she said. 

Among 21,525 people who had COVID-19 and had symptoms, tiredness, headache and muscle aches or muscle weakness were the most common ongoing symptoms. 

Loss of smell was almost nine times more likely in this group compared to the never-infected group in one analysis where researchers controlled for other possible factors. The risk for loss of taste was almost six times greater, followed by risk of breathlessness at three times higher. 

Long COVID risk was highest after a severe original infection and among older people, women, Black, and South Asian populations, people with socioeconomic disadvantages, and those with more than one underlying health condition.

Adding up the 6% with no recovery after 18 months and 42% with partial recovery means that between 6 and 18 months following symptomatic coronavirus infection, almost half of those infected still experience persistent symptoms.
 

Vaccination validated

On the plus side, people vaccinated against COVID-19 before getting infected had a lower risk for some persistent symptoms. In addition, Dr. Pell and colleagues found no evidence that people who experienced asymptomatic infection were likely to experience long COVID symptoms or challenges with activities of daily living. 

The findings of the Long-COVID in Scotland Study (Long-CISS) were published in the journal Nature Communications.
 

‘More long COVID than ever before’

“Unfortunately, these long COVID symptoms are not getting better as the cases of COVID get milder,” said Thomas Gut, DO, medical director for the post-COVID recovery program at Staten Island (N.Y.) University Hospital. “Quite the opposite – this infection has become so common in a community because it’s so mild and spreading so rapidly that we’re seeing more long COVID symptoms than ever before.” 

Although most patients he sees with long COVID resolve their symptoms within 3-6 months, “We do see some patients who require short-term disability because their symptoms continue past 6 months and out to 2 years,” said Dr. Gut, a hospitalist at Staten Island University Hospital, a member hospital of Northwell Health.

Patients with fatigue and neurocognitive symptoms “have a very tough time going back to work. Short-term disability gives them the time and finances to pursue specialty care with cardiology, pulmonary, and neurocognitive testing,” he said.
 

Support the whole person

The burden of living with long COVID goes beyond the persistent symptoms. “Long COVID can have wide-ranging impacts – not only on health but also quality of life and activities of daily living [including] work, mobility, self-care and more,” Dr. Pell said. “So, people with long COVID need support relevant to their individual needs and this may extend beyond the health care sector, for example including social services, school or workplace.”

Still,  Lisa Penziner, RN, founder of the COVID Long Haulers Support Group in Westchester and Long Island, N.Y., said while people with the most severe cases of COVID-19 tended to have the worst long COVID symptoms, they’re not the only ones. 

“We saw many post-COVID members who had mild cases and their long-haul symptoms were worse weeks later than the virus itself,” said Md. Penziner. 

She estimates that 80%-90% of her support group members recover within 6 months. “However, there are others who were experiencing symptoms for much longer.”

Respiratory treatment, physical therapy, and other follow-up doctor visits are common after 6 months, for example. 

“Additionally, there is a mental health component to recovery as well, meaning that the patient must learn to live while experiencing lingering, long-haul COVID symptoms in work and daily life,” said Ms. Penziner, director of special projects at North Westchester Restorative Therapy & Nursing. 

In addition to ongoing medical care, people with long COVID need understanding, she said.

“While long-haul symptoms do not happen to everyone, it is proven that many do experience long-haul symptoms, and the support of the community in understanding is important.”
 

Limitations of the study

Dr. Pell and colleagues noted some strengths and weaknesses to their study. For example, “as a general population study, our findings provide a better indication of the overall risk and burden of long COVID than hospitalized cohorts,” they noted. 

Also, the Scottish population is 96% White, so other long COVID studies with more diverse participants are warranted. 

Another potential weakness is the response rate of 16% among those invited to participate in the study, which Dr. Pell and colleagues addressed: “Our cohort included a large sample (33,281) of people previously infected and the response rate of 16% overall and 20% among people who had symptomatic infection was consistent with previous studies that have used SMS text invitations as the sole method of recruitment.”

“We tell patients this should last 3-6 months, but some patients have longer recovery periods,” Dr. Gut said. “We’re here for them. We have a lot of services available to help get them through the recovery process, and we have a lot of options to help support them.”

“What we found most helpful is when there is peer-to-peer support, reaffirming to the member that they are not alone in the long-haul battle, which has been a major benefit of the support group,” Ms. Penziner said.

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

Foods for thought: Menstrual cramp prevention

For those who menstruate, it’s typical for that time of the month to bring cravings for things that may give a serotonin boost that eases the rise in stress hormones. Chocolate and other foods high in sugar fall into that category, but they could actually be adding to the problem.

Carlo107/Getty Images

About 90% of adolescent girls have menstrual pain, and it’s the leading cause of school absences for the demographic. Muscle relaxers and PMS pills are usually the recommended solution to alleviating menstrual cramps, but what if the patient doesn’t want to take any medicine?

Serah Sannoh of Rutgers University wanted to find another way to relieve her menstrual pains. The literature review she presented at the annual meeting of the North American Menopause Society found multiple studies that examined dietary patterns that resulted in menstrual pain.

In Ms. Sannoh’s analysis, she looked at how certain foods have an effect on cramps. Do they contribute to the pain or reduce it? Diets high in processed foods, oils, sugars, salt, and omega-6 fatty acids promote inflammation in the muscles around the uterus. Thus, cramps.

The answer, sometimes, is not to add a medicine but to change our daily practices, she suggested. Foods high in omega-3 fatty acids helped reduce pain, and those who practiced a vegan diet had the lowest muscle inflammation rates. So more salmon and fewer Swedish Fish.
 

Stage 1 of the robot apocalypse is already upon us

The mere mention of a robot apocalypse is enough to conjure images of terrifying robot soldiers with Austrian accents harvesting and killing humanity while the survivors live blissfully in a simulation and do low-gravity kung fu with high-profile Hollywood actors. They’ll even take over the navy.

Inderpreet/Pixahive

Reality is often less exciting than the movies, but rest assured, the robots will not be denied their dominion of Earth. Our future robot overlords are simply taking a more subtle, less dramatic route toward their ultimate subjugation of mankind: They’re making us all sad and burned out.

The research pulls from work conducted in multiple countries to paint a picture of a humanity filled with anxiety about jobs as robotic automation grows more common. In India, a survey of automobile manufacturing works showed that working alongside industrial robots was linked with greater reports of burnout and workplace incivility. In Singapore, a group of college students randomly assigned to read one of three articles – one about the use of robots in business, a generic article about robots, or an article unrelated to robots – were then surveyed about their job security concerns. Three guesses as to which group was most worried.

In addition, the researchers analyzed 185 U.S. metropolitan areas for robot prevalence alongside use of job-recruiting websites and found that the more robots a city used, the more common job searches were. Unemployment rates weren’t affected, suggesting people had job insecurity because of robots. Sure, there could be other, nonrobotic reasons for this, but that’s no fun. We’re here because we fear our future android rulers.

It’s not all doom and gloom, fortunately. In an online experiment, the study authors found that self-affirmation exercises, such as writing down characteristics or values important to us, can overcome the existential fears and lessen concern about robots in the workplace. One of the authors noted that, while some fear is justified, “media reports on new technologies like robots and algorithms tend to be apocalyptic in nature, so people may develop an irrational fear about them.”

Oops. Our bad.
 

Apocalypse, stage 2: Leaping oral superorganisms

The terms of our secret agreement with the shadowy-but-powerful dental-industrial complex stipulate that LOTME can only cover tooth-related news once a year. This is that once a year.

Penn Dental Medicine

Since we’ve already dealt with a robot apocalypse, how about a sci-fi horror story? A story with a “cross-kingdom partnership” in which assemblages of bacteria and fungi perform feats greater than either could achieve on its own. A story in which new microscopy technologies allow “scientists to visualize the behavior of living microbes in real time,” according to a statement from the University of Pennsylvania, Philadelphia.

While looking at saliva samples from toddlers with severe tooth decay, lead author Zhi Ren and associates “noticed the bacteria and fungi forming these assemblages and developing motions we never thought they would possess: a ‘walking-like’ and ‘leaping-like’ mobility. … It’s almost like a new organism – a superorganism – with new functions,” said senior author Hyun Koo, DDS, PhD, of Penn Dental Medicine.

Did he say “mobility”? He did, didn’t he?

To study these alleged superorganisms, they set up a laboratory system “using the bacteria, fungi, and a tooth-like material, all incubated in human saliva,” the university explained.

“Incubated in human saliva.” There’s a phrase you don’t see every day.

It only took a few hours for the investigators to observe the bacterial/fungal assemblages making leaps of more than 100 microns across the tooth-like material. “That is more than 200 times their own body length,” Dr. Ren said, “making them even better than most vertebrates, relative to body size. For example, tree frogs and grasshoppers can leap forward about 50 times and 20 times their own body length, respectively.”

So, will it be the robots or the evil superorganisms? Let us give you a word of advice: Always bet on bacteria.

Foods for thought: Menstrual cramp prevention

For those who menstruate, it’s typical for that time of the month to bring cravings for things that may give a serotonin boost that eases the rise in stress hormones. Chocolate and other foods high in sugar fall into that category, but they could actually be adding to the problem.

Carlo107/Getty Images

About 90% of adolescent girls have menstrual pain, and it’s the leading cause of school absences for the demographic. Muscle relaxers and PMS pills are usually the recommended solution to alleviating menstrual cramps, but what if the patient doesn’t want to take any medicine?

Serah Sannoh of Rutgers University wanted to find another way to relieve her menstrual pains. The literature review she presented at the annual meeting of the North American Menopause Society found multiple studies that examined dietary patterns that resulted in menstrual pain.

In Ms. Sannoh’s analysis, she looked at how certain foods have an effect on cramps. Do they contribute to the pain or reduce it? Diets high in processed foods, oils, sugars, salt, and omega-6 fatty acids promote inflammation in the muscles around the uterus. Thus, cramps.

The answer, sometimes, is not to add a medicine but to change our daily practices, she suggested. Foods high in omega-3 fatty acids helped reduce pain, and those who practiced a vegan diet had the lowest muscle inflammation rates. So more salmon and fewer Swedish Fish.
 

Stage 1 of the robot apocalypse is already upon us

The mere mention of a robot apocalypse is enough to conjure images of terrifying robot soldiers with Austrian accents harvesting and killing humanity while the survivors live blissfully in a simulation and do low-gravity kung fu with high-profile Hollywood actors. They’ll even take over the navy.

Inderpreet/Pixahive

Reality is often less exciting than the movies, but rest assured, the robots will not be denied their dominion of Earth. Our future robot overlords are simply taking a more subtle, less dramatic route toward their ultimate subjugation of mankind: They’re making us all sad and burned out.

The research pulls from work conducted in multiple countries to paint a picture of a humanity filled with anxiety about jobs as robotic automation grows more common. In India, a survey of automobile manufacturing works showed that working alongside industrial robots was linked with greater reports of burnout and workplace incivility. In Singapore, a group of college students randomly assigned to read one of three articles – one about the use of robots in business, a generic article about robots, or an article unrelated to robots – were then surveyed about their job security concerns. Three guesses as to which group was most worried.

In addition, the researchers analyzed 185 U.S. metropolitan areas for robot prevalence alongside use of job-recruiting websites and found that the more robots a city used, the more common job searches were. Unemployment rates weren’t affected, suggesting people had job insecurity because of robots. Sure, there could be other, nonrobotic reasons for this, but that’s no fun. We’re here because we fear our future android rulers.

It’s not all doom and gloom, fortunately. In an online experiment, the study authors found that self-affirmation exercises, such as writing down characteristics or values important to us, can overcome the existential fears and lessen concern about robots in the workplace. One of the authors noted that, while some fear is justified, “media reports on new technologies like robots and algorithms tend to be apocalyptic in nature, so people may develop an irrational fear about them.”

Oops. Our bad.
 

Apocalypse, stage 2: Leaping oral superorganisms

The terms of our secret agreement with the shadowy-but-powerful dental-industrial complex stipulate that LOTME can only cover tooth-related news once a year. This is that once a year.

Penn Dental Medicine

Since we’ve already dealt with a robot apocalypse, how about a sci-fi horror story? A story with a “cross-kingdom partnership” in which assemblages of bacteria and fungi perform feats greater than either could achieve on its own. A story in which new microscopy technologies allow “scientists to visualize the behavior of living microbes in real time,” according to a statement from the University of Pennsylvania, Philadelphia.

While looking at saliva samples from toddlers with severe tooth decay, lead author Zhi Ren and associates “noticed the bacteria and fungi forming these assemblages and developing motions we never thought they would possess: a ‘walking-like’ and ‘leaping-like’ mobility. … It’s almost like a new organism – a superorganism – with new functions,” said senior author Hyun Koo, DDS, PhD, of Penn Dental Medicine.

Did he say “mobility”? He did, didn’t he?

To study these alleged superorganisms, they set up a laboratory system “using the bacteria, fungi, and a tooth-like material, all incubated in human saliva,” the university explained.

“Incubated in human saliva.” There’s a phrase you don’t see every day.

It only took a few hours for the investigators to observe the bacterial/fungal assemblages making leaps of more than 100 microns across the tooth-like material. “That is more than 200 times their own body length,” Dr. Ren said, “making them even better than most vertebrates, relative to body size. For example, tree frogs and grasshoppers can leap forward about 50 times and 20 times their own body length, respectively.”

So, will it be the robots or the evil superorganisms? Let us give you a word of advice: Always bet on bacteria.

Foods for thought: Menstrual cramp prevention

For those who menstruate, it’s typical for that time of the month to bring cravings for things that may give a serotonin boost that eases the rise in stress hormones. Chocolate and other foods high in sugar fall into that category, but they could actually be adding to the problem.

Carlo107/Getty Images

About 90% of adolescent girls have menstrual pain, and it’s the leading cause of school absences for the demographic. Muscle relaxers and PMS pills are usually the recommended solution to alleviating menstrual cramps, but what if the patient doesn’t want to take any medicine?

Serah Sannoh of Rutgers University wanted to find another way to relieve her menstrual pains. The literature review she presented at the annual meeting of the North American Menopause Society found multiple studies that examined dietary patterns that resulted in menstrual pain.

In Ms. Sannoh’s analysis, she looked at how certain foods have an effect on cramps. Do they contribute to the pain or reduce it? Diets high in processed foods, oils, sugars, salt, and omega-6 fatty acids promote inflammation in the muscles around the uterus. Thus, cramps.

The answer, sometimes, is not to add a medicine but to change our daily practices, she suggested. Foods high in omega-3 fatty acids helped reduce pain, and those who practiced a vegan diet had the lowest muscle inflammation rates. So more salmon and fewer Swedish Fish.
 

Stage 1 of the robot apocalypse is already upon us

The mere mention of a robot apocalypse is enough to conjure images of terrifying robot soldiers with Austrian accents harvesting and killing humanity while the survivors live blissfully in a simulation and do low-gravity kung fu with high-profile Hollywood actors. They’ll even take over the navy.

Inderpreet/Pixahive

Reality is often less exciting than the movies, but rest assured, the robots will not be denied their dominion of Earth. Our future robot overlords are simply taking a more subtle, less dramatic route toward their ultimate subjugation of mankind: They’re making us all sad and burned out.

The research pulls from work conducted in multiple countries to paint a picture of a humanity filled with anxiety about jobs as robotic automation grows more common. In India, a survey of automobile manufacturing works showed that working alongside industrial robots was linked with greater reports of burnout and workplace incivility. In Singapore, a group of college students randomly assigned to read one of three articles – one about the use of robots in business, a generic article about robots, or an article unrelated to robots – were then surveyed about their job security concerns. Three guesses as to which group was most worried.

In addition, the researchers analyzed 185 U.S. metropolitan areas for robot prevalence alongside use of job-recruiting websites and found that the more robots a city used, the more common job searches were. Unemployment rates weren’t affected, suggesting people had job insecurity because of robots. Sure, there could be other, nonrobotic reasons for this, but that’s no fun. We’re here because we fear our future android rulers.

It’s not all doom and gloom, fortunately. In an online experiment, the study authors found that self-affirmation exercises, such as writing down characteristics or values important to us, can overcome the existential fears and lessen concern about robots in the workplace. One of the authors noted that, while some fear is justified, “media reports on new technologies like robots and algorithms tend to be apocalyptic in nature, so people may develop an irrational fear about them.”

Oops. Our bad.
 

Apocalypse, stage 2: Leaping oral superorganisms

The terms of our secret agreement with the shadowy-but-powerful dental-industrial complex stipulate that LOTME can only cover tooth-related news once a year. This is that once a year.

Penn Dental Medicine

Since we’ve already dealt with a robot apocalypse, how about a sci-fi horror story? A story with a “cross-kingdom partnership” in which assemblages of bacteria and fungi perform feats greater than either could achieve on its own. A story in which new microscopy technologies allow “scientists to visualize the behavior of living microbes in real time,” according to a statement from the University of Pennsylvania, Philadelphia.

While looking at saliva samples from toddlers with severe tooth decay, lead author Zhi Ren and associates “noticed the bacteria and fungi forming these assemblages and developing motions we never thought they would possess: a ‘walking-like’ and ‘leaping-like’ mobility. … It’s almost like a new organism – a superorganism – with new functions,” said senior author Hyun Koo, DDS, PhD, of Penn Dental Medicine.

Did he say “mobility”? He did, didn’t he?

To study these alleged superorganisms, they set up a laboratory system “using the bacteria, fungi, and a tooth-like material, all incubated in human saliva,” the university explained.

“Incubated in human saliva.” There’s a phrase you don’t see every day.

It only took a few hours for the investigators to observe the bacterial/fungal assemblages making leaps of more than 100 microns across the tooth-like material. “That is more than 200 times their own body length,” Dr. Ren said, “making them even better than most vertebrates, relative to body size. For example, tree frogs and grasshoppers can leap forward about 50 times and 20 times their own body length, respectively.”

So, will it be the robots or the evil superorganisms? Let us give you a word of advice: Always bet on bacteria.

Counting calories should not be the focus of weight-loss strategies for children with obesity, according to an expert who said pediatricians need to change the way they discuss weight with their patients.

During a plenary session of the American Academy of Pediatrics National Conference, Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, N.C., said pediatricians should recognize the behavioral, physical, environmental, and genetic factors that contribute to obesity. For instance, food deserts are on the rise, and they undermine the ability of parents to feed their children healthy meals. In addition, more children are less physically active.

“Obesity is a lot more complex than calories in, calories out,” Dr. Skelton said. “We choose to treat issues of obesity as personal responsibility – ‘you did this to yourself’ – but when you look at how we move around and live our lives, our food systems, our policies, the social and environmental changes have caused shifts in our behavior.”

According to Dr. Skelton, bias against children with obesity can harm their self-image and weaken their motivations for losing weight. In addition, doctors may change how they deliver care on the basis of stereotypes regarding obese children. These stereotypes are often reinforced in media portrayals, Dr. Skelton said.

“When children or when adults who have excess weight or obesity are portrayed, they are portrayed typically in a negative fashion,” Dr. Skelton said. “There’s increasing evidence that weight bias and weight discrimination are increasing the morbidity we see in patients who develop obesity.”

For many children with obesity, visits to the pediatrician often center on weight, regardless of the reason for the appointment. Weight stigma and bias on the part of health care providers can increase stress, as well as adverse health outcomes in children, according to a 2019 study (Curr Opin Endocrinol Diabetes Obes. 2019 Feb 1. doi: 10.1097/MED.0000000000000453). Dr. Skelton recommended that pediatricians listen to their patients’ concerns and make a personalized care plan.

Dr. Skelton said doctors can pull from projects such as Health at Every Size, which offers templates for personalized health plans for children with obesity. It has a heavy focus on a weight-neutral approach to pediatric health.

“There are various ways to manage weight in a healthy and safe way,” Dr. Skelton said.

Evidence-based methods of treating obesity include focusing on health and healthy behaviors rather than weight and using the body mass index as a screening tool for further conversations about overall health, rather than as an indicator of health based on weight.

Dr. Skelton also encouraged pediatricians to be on the alert for indicators of disordered eating, which can include dieting, teasing, or talking excessively about weight at home and can involve reading misinformation about dieting online.

“Your job is to educate people on the dangers of following unscientific information online,” Dr. Skelton said. “We can address issues of weight health in a way that is patient centered and is very safe, without unintended consequences.” Brooke Sweeney, MD, professor of internal medicine and pediatrics at University of Missouri–Kansas City, said problems with weight bias in society and in clinical practice can lead to false assumptions about people who have obesity.

“It’s normal to gain adipose, or fat tissue, at different times in life, during puberty or pregnancy, and some people normally gain more weight than others,” Dr. Sweeney said.

The body will try to maintain a weight set point. That set point is influenced by many factors, such as genetics, environment, and lifestyle.

“When you lose weight, your body tries to get you back to the set point, decreasing energy expenditure and increasing hunger and reward pathways,” she said. “We have gained so much knowledge through research to better understand the pathophysiology of obesity, and we are making good progress on improving advanced treatments for increased weight in children.”

Dr. Skelton reports no relevant financial relationships.

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

Counting calories should not be the focus of weight-loss strategies for children with obesity, according to an expert who said pediatricians need to change the way they discuss weight with their patients.

During a plenary session of the American Academy of Pediatrics National Conference, Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, N.C., said pediatricians should recognize the behavioral, physical, environmental, and genetic factors that contribute to obesity. For instance, food deserts are on the rise, and they undermine the ability of parents to feed their children healthy meals. In addition, more children are less physically active.

“Obesity is a lot more complex than calories in, calories out,” Dr. Skelton said. “We choose to treat issues of obesity as personal responsibility – ‘you did this to yourself’ – but when you look at how we move around and live our lives, our food systems, our policies, the social and environmental changes have caused shifts in our behavior.”

According to Dr. Skelton, bias against children with obesity can harm their self-image and weaken their motivations for losing weight. In addition, doctors may change how they deliver care on the basis of stereotypes regarding obese children. These stereotypes are often reinforced in media portrayals, Dr. Skelton said.

“When children or when adults who have excess weight or obesity are portrayed, they are portrayed typically in a negative fashion,” Dr. Skelton said. “There’s increasing evidence that weight bias and weight discrimination are increasing the morbidity we see in patients who develop obesity.”

For many children with obesity, visits to the pediatrician often center on weight, regardless of the reason for the appointment. Weight stigma and bias on the part of health care providers can increase stress, as well as adverse health outcomes in children, according to a 2019 study (Curr Opin Endocrinol Diabetes Obes. 2019 Feb 1. doi: 10.1097/MED.0000000000000453). Dr. Skelton recommended that pediatricians listen to their patients’ concerns and make a personalized care plan.

Dr. Skelton said doctors can pull from projects such as Health at Every Size, which offers templates for personalized health plans for children with obesity. It has a heavy focus on a weight-neutral approach to pediatric health.

“There are various ways to manage weight in a healthy and safe way,” Dr. Skelton said.

Evidence-based methods of treating obesity include focusing on health and healthy behaviors rather than weight and using the body mass index as a screening tool for further conversations about overall health, rather than as an indicator of health based on weight.

Dr. Skelton also encouraged pediatricians to be on the alert for indicators of disordered eating, which can include dieting, teasing, or talking excessively about weight at home and can involve reading misinformation about dieting online.

“Your job is to educate people on the dangers of following unscientific information online,” Dr. Skelton said. “We can address issues of weight health in a way that is patient centered and is very safe, without unintended consequences.” Brooke Sweeney, MD, professor of internal medicine and pediatrics at University of Missouri–Kansas City, said problems with weight bias in society and in clinical practice can lead to false assumptions about people who have obesity.

“It’s normal to gain adipose, or fat tissue, at different times in life, during puberty or pregnancy, and some people normally gain more weight than others,” Dr. Sweeney said.

The body will try to maintain a weight set point. That set point is influenced by many factors, such as genetics, environment, and lifestyle.

“When you lose weight, your body tries to get you back to the set point, decreasing energy expenditure and increasing hunger and reward pathways,” she said. “We have gained so much knowledge through research to better understand the pathophysiology of obesity, and we are making good progress on improving advanced treatments for increased weight in children.”

Dr. Skelton reports no relevant financial relationships.

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

Counting calories should not be the focus of weight-loss strategies for children with obesity, according to an expert who said pediatricians need to change the way they discuss weight with their patients.

During a plenary session of the American Academy of Pediatrics National Conference, Joseph A. Skelton, MD, professor of pediatrics at Wake Forest University School of Medicine, Winston-Salem, N.C., said pediatricians should recognize the behavioral, physical, environmental, and genetic factors that contribute to obesity. For instance, food deserts are on the rise, and they undermine the ability of parents to feed their children healthy meals. In addition, more children are less physically active.

“Obesity is a lot more complex than calories in, calories out,” Dr. Skelton said. “We choose to treat issues of obesity as personal responsibility – ‘you did this to yourself’ – but when you look at how we move around and live our lives, our food systems, our policies, the social and environmental changes have caused shifts in our behavior.”

According to Dr. Skelton, bias against children with obesity can harm their self-image and weaken their motivations for losing weight. In addition, doctors may change how they deliver care on the basis of stereotypes regarding obese children. These stereotypes are often reinforced in media portrayals, Dr. Skelton said.

“When children or when adults who have excess weight or obesity are portrayed, they are portrayed typically in a negative fashion,” Dr. Skelton said. “There’s increasing evidence that weight bias and weight discrimination are increasing the morbidity we see in patients who develop obesity.”

For many children with obesity, visits to the pediatrician often center on weight, regardless of the reason for the appointment. Weight stigma and bias on the part of health care providers can increase stress, as well as adverse health outcomes in children, according to a 2019 study (Curr Opin Endocrinol Diabetes Obes. 2019 Feb 1. doi: 10.1097/MED.0000000000000453). Dr. Skelton recommended that pediatricians listen to their patients’ concerns and make a personalized care plan.

Dr. Skelton said doctors can pull from projects such as Health at Every Size, which offers templates for personalized health plans for children with obesity. It has a heavy focus on a weight-neutral approach to pediatric health.

“There are various ways to manage weight in a healthy and safe way,” Dr. Skelton said.

Evidence-based methods of treating obesity include focusing on health and healthy behaviors rather than weight and using the body mass index as a screening tool for further conversations about overall health, rather than as an indicator of health based on weight.

Dr. Skelton also encouraged pediatricians to be on the alert for indicators of disordered eating, which can include dieting, teasing, or talking excessively about weight at home and can involve reading misinformation about dieting online.

“Your job is to educate people on the dangers of following unscientific information online,” Dr. Skelton said. “We can address issues of weight health in a way that is patient centered and is very safe, without unintended consequences.” Brooke Sweeney, MD, professor of internal medicine and pediatrics at University of Missouri–Kansas City, said problems with weight bias in society and in clinical practice can lead to false assumptions about people who have obesity.

“It’s normal to gain adipose, or fat tissue, at different times in life, during puberty or pregnancy, and some people normally gain more weight than others,” Dr. Sweeney said.

The body will try to maintain a weight set point. That set point is influenced by many factors, such as genetics, environment, and lifestyle.

“When you lose weight, your body tries to get you back to the set point, decreasing energy expenditure and increasing hunger and reward pathways,” she said. “We have gained so much knowledge through research to better understand the pathophysiology of obesity, and we are making good progress on improving advanced treatments for increased weight in children.”

Dr. Skelton reports no relevant financial relationships.

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

Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist. 

“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”

Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
 

Spectrums of disease

Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.

With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.  

Beckwith-Wiedemann syndrome is a prime example.  The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.

Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.

To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.

Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.

Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
 

Spotting a “compilation of features”

Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.

For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”

Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.

One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.

The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.

In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.

She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.

Dr. Kalish reported no relevant financial relationships.

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

Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist. 

“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”

Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
 

Spectrums of disease

Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.

With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.  

Beckwith-Wiedemann syndrome is a prime example.  The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.

Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.

To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.

Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.

Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
 

Spotting a “compilation of features”

Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.

For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”

Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.

One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.

The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.

In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.

She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.

Dr. Kalish reported no relevant financial relationships.

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

Jennifer Kalish, MD, PhD, fields as many as 10 inquiries a month from pediatricians who spot an unusual feature during a clinical exam, and wonder if they should refer the family to a geneticist. 

“There are hundreds of rare disorders, and for a pediatrician, they can be hard to recognize,” Dr. Kalish said. “That’s why we’re here as geneticists – to partner so that we can help.”

Pediatricians play a key role in spotting signs of rare genetic diseases, but may need guidance for recognizing the more subtle presentations of a disorder, according to Dr. Kalish, a geneticist and director of the Beckwith-Wiedemann Syndrome Clinic at Children’s Hospital of Philadelphia, who spoke at the American Academy of Pediatrics National Conference.
 

Spectrums of disease

Pediatricians may struggle with deciding whether to make a referral, in part because genetic syndromes “do not always look like the textbook,” she said.

With many conditions, “we’re starting to understand that there’s really a spectrum of how affected versus less affected one can be,” by genetic and epigenetic changes, which have led to recognition that many cases are more subtle and harder to diagnose, she said.  

Beckwith-Wiedemann syndrome is a prime example.  The overgrowth disorder affects an estimated 1 in 10,340 infants, and is associated with a heightened risk of Wilms tumors, a form of kidney cancer, and hepatoblastomas. Children diagnosed with these conditions typically undergo frequent screenings to detect tumors to jumpstart treatment.

Some researchers believe Beckwith-Wiedemann syndrome is underdiagnosed because it can present in many different ways because of variations in the distributions of affected cells in the body, known as mosaicism.

To address the complexity, Dr. Kalish guided development of a scoring system for determining whether molecular testing is warranted. Primary features such as an enlarged tongue and lateralized overgrowth carry more points, whereas suggestive features like ear creases or large birth weight carry fewer points.

Diagnostic advances have occurred for other syndromes, as well. For example, researchers have created a scoring system for Russell-Silver syndrome, a less common disorder characterized by slow growth before and after birth, in which mosaicism is also present.

Early diagnosis and intervention of Russell-Silver syndrome can ensure that patients grow to their maximum potential and address problems such as feeding issues.
 

Spotting a “compilation of features”

Although tools are available, Dr. Kalish said pediatricians don’t need to make a diagnosis, and instead can refer patients to a geneticist after recognizing clinical features that hint at a genetic etiology.

For pediatricians, the process of deciding whether to refer a patient to a geneticist may entail ruling out nongenetic causes, considering patient and family history, and ultimately deciding whether there is a “compilation of features” that falls outside the norm, she said. Unfortunately, she added, there’s “not a simple list I could just hand out saying, ‘If you see these things, call me.’ ”

Dr. Kalish said pediatricians should be aware that two children with similar features can have different syndromes. She presented case studies of two infants, who both had enlarged tongues and older mothers.

One child had hallmarks that pointed to Beckwith-Wiedemann syndrome: conception with in vitro fertilization, length in the 98th percentile, a long umbilical cord, nevus simplex birthmarks, and labial and leg asymmetry.

The other baby had features aligned with Down syndrome: a heart murmur, upward slanting eyes, and a single crease on the palm.

In some cases, isolated features such as the shape, slant, or spacing of eyes, or the presence of creases on the ears, may simply be familial or inherited traits, Dr. Kalish said.

She noted that “there’s been a lot of work in genetics in the past few years to show what syndromes look like” in diverse populations. The American Journal of Medical Genetics Part A has published a series of reports on the topic.

Dr. Kalish reported no relevant financial relationships.

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