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Hepatologist finds purpose as health equity advocate for LGBTQI+
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
Sonali Paul, MD, once thought she was an anomaly in the world of medicine. “As I was going through training, I didn’t think others like me existed, a gay South Asian transplant hepatologist. I certainly didn’t have mentors that looked like me. I didn’t have anyone to look up to,” she said.
Fighting to promote health care equity in the LGBTQI+ population has been a cornerstone of her career. As cofounder and an executive board member of Rainbows in Gastro, a sexual and gender minorities affinity group that builds community among LGBTQI+ medical trainees and physicians in gastroenterology, Dr. Paul often goes into the community to promote open discussions about health equity in sexual and gender minority populations.
“Our mission is CHARM: community, healing, advocacy, research, and mentorship,” said Dr. Paul, a transplant hepatologist with the University of Chicago Medicine with a specific niche within fatty liver disease and obesity medicine. She serves as an associate program director for the Internal Medicine Residency Program specifically for diversity, equity, and inclusion.
In 2022 she received the University of Chicago’s Department of Medicine Diversity Award.
Rainbows in Gastro has shown trainees they can be open about their sexual orientation and gender identity without fear of retribution. “I’ve had medical students and residents come to me and say they were going to go into endocrine or some other field because they thought it was more gay friendly, until they saw our group and the work we’re doing,” Dr. Paul said.
In an interview, she talks more about her two key passions: reducing disparities and promoting health equity.
Q: You presented “Embrace the Rainbow: Creating Inclusive LGBTQ+ Spaces in Medicine” at the University of Chicago Medicine Grand Rounds. What were some of the key takeaways of that presentation?
Dr. Paul: One is education. Knowing the history of the LGBT community and how marginalization and discrimination affects the individual coming into that clinic is important. Having little things like pronoun badges or a rainbow flag, having nondiscrimination policies that include sexual orientation, gender identity that are displayed in the clinics, are very small things that seem almost trivial to some people. But I can tell you for myself, it matters if I walk into a door and there’s a rainbow flag there. I feel immediately safer.
Q: What are your hopes and aspirations for the field of GI moving forward?
Dr. Paul: I didn’t learn about social determinants of health in medical school, but more and more I think we’re starting to pivot and really look at those things. I hope GI and hepatology continues to do that.
For me, it’s looking at everything through a health disparities lens, seeing the health disparities across communities and finding solutions to mitigate them. How do we get people access to transplant for all our patients, and really examining the social determinants of health in the health care we provide?
Q: Your clinical focus has been on nonalcoholic fatty liver disease. Can you tell me how you got interested in that area of medicine?
Dr. Paul: There’s been a name change for the disease itself. It’s now metabolic dysfunction-associated steatotic liver disease (MASLD). I got interested from an obesity medicine perspective. I thought the liver pathology was interesting but I wanted to approach it from a different kind of perspective and not just focus on the liver, but also the metabolic factors.
I practice from that kind of lens: Looking at a lot of the metabolic comorbidities that happen with fatty liver disease to help patients with weight loss.
Q: What do you think about the new weight loss drugs?
Dr. Paul: I think they’re very effective. They’re obviously very popular. Weight loss is a really hard thing and I think they are really changing the game. A newer one that was just approved, tirzepatide (Zepbound, Lilly) resulted in up to 20% body weight loss. I think if there’s a medicine that we can give to avoid surgery for some people, I think that’s great. I think what is quite disheartening is insurance access to the medications.
Q: Is there any type of research you’re doing in this area right now?
Dr. Paul: I’m interested in the changes in fatty liver with gender-affirming hormone therapy with estrogen and testosterone, an area that’s never been studied.
Q: Describe how you would spend a free Saturday afternoon.
Dr. Paul: With my wife, my 9-year-old son, and two dogs. One of our favorite places to go is the Lincoln Park Zoo. We go there, especially over the summer, sometimes every week just to walk around. And, my son loves animals. Or, play with our dogs.
LIGHTNING ROUND
What is your favorite junk food?
Doritos
What is your favorite holiday?
Thanksgiving
Is there a book that you reread often?
“Interpreter of Maladies” by Jhumpa Lahiri
What is your favorite movie genre?
Comedy
Are you an introvert or extrovert?
Somewhere in the middle.
H pylori Infection Linked to Increased Alzheimer’s Risk
TOPLINE:
results of a large and lengthy population-based study suggest.
METHODOLOGY:
- Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
- The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
- Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.
TAKEAWAY:
- Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
- The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
- Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
- The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).
IN PRACTICE:
“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.
SOURCE:
The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.
DISCLOSURES:
The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.
Pauline Anderson has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
results of a large and lengthy population-based study suggest.
METHODOLOGY:
- Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
- The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
- Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.
TAKEAWAY:
- Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
- The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
- Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
- The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).
IN PRACTICE:
“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.
SOURCE:
The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.
DISCLOSURES:
The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.
Pauline Anderson has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
TOPLINE:
results of a large and lengthy population-based study suggest.
METHODOLOGY:
- Researchers identified all cases with a first-time diagnosis of AD and matched each AD case to up to 40 AD-free control cases on the basis of age, sex, cohort entry date, and duration of follow-up.
- The exposure of interest was CAHPI, defined based on an algorithm using clinical guidelines and recommendations on the management of H pylori (HP) infection, with researchers focusing on infected individuals presenting with symptoms or developing serious complications from the infection.
- Researchers performed several sensitivity analyses, which included repeating the primary analysis using alternate lag periods, restricting the cohort to participants with AD (not vascular, alcoholic, and unspecified dementia), and using salmonellosis, an infection not previously associated with AD, as a negative control exposure.
TAKEAWAY:
- Compared with no exposure to CAHPI, exposure to CAHPI was associated with a moderately increased risk for AD (odds ratio [OR], 1.11; 95% CI, 1.01-1.21), with no major effect modification by demographics or socioeconomic status.
- The increased risk peaked 7.3-10.8 years after CAHPI onset (OR, 1.24; 95% CI, 1.05-1.47) before decreasing.
- Sensitivity analyses yielded findings that were overall consistent with those of the primary analysis.
- The analysis with salmonellosis as a negative control exposure showed no association with the risk for AD (OR, 1.03; 95% CI, 0.82-1.29).
IN PRACTICE:
“These results support the notion of HP infection as a potential modifiable risk factor of AD” and “pave the way for future randomized controlled trials that would assess the impact and cost-effectiveness of population-based targeted interventions such as individualized HP eradication programs, on the development of AD,” the authors write.
SOURCE:
The study was conducted by Antonios Douros, Department of Medicine, and Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Quebec, Canada, and colleagues. It was published online in Alzheimer’s & Dementia.
LIMITATIONS:
Given the observational nature of the study, residual confounding is possible. Because the exposure definition was on the basis of CAHPI recorded by general practitioners, exposure misclassification due to symptomatic patients not seeking primary care is possible, as is outcome misclassification. The authors can’t rule out the possibility of an association between asymptomatic H pylori infection and AD risk.
DISCLOSURES:
The study received funding from the Canadian Institutes of Health Research. Douros has no relevant conflicts of interest; see paper for disclosures of other authors.
Pauline Anderson has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
What Makes Patients Vulnerable to Delusions of Parasitosis?
, reported researchers in a small retrospective case-control study.
Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.
“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”
To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.
Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).
In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”
They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.
“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.
Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.
“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”
The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.
, reported researchers in a small retrospective case-control study.
Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.
“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”
To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.
Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).
In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”
They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.
“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.
Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.
“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”
The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.
, reported researchers in a small retrospective case-control study.
Delusions of parasitosis (DOP) affects mostly middle-aged women and has associations with renal failure and some medications, wrote corresponding author Colleen Reisz, MD, a dermatologist with the department of internal medicine at the University of Missouri–Kansas City School of Medicine, and her coauthors. The study was published online December 15, 2023, in the Journal of the American Academy of Dermatology.
“We hypothesize that vulnerability to DOP emerges when multiple factors combine, such as age, sex, medications, and changes in [drug] clearance capacity,” Dr. Reisz and her coauthors wrote. “Changes in health care, such as the dramatic increase in stimulant prescriptions and alternatives to opioids in pain management, may be contributing to off target drug effects on the brain.”
To test their hypothesis, the researchers conducted a case-control study of biometric and pharmaceutical data from 34 patients with DOP which they compared to an age-matched control group of 53 women presenting with a dermatitis above the clavicle from a general dermatology practice between 2012 and 2020. They de-identified the data and performed statistical analysis on variables that included biometric data and intake of pharmaceuticals and nutraceuticals. Polypharmacy was defined as five or more drugs.
Of the 34 patients with DOP, 27 were women with a mean age of 58 years and 7 were men with a mean age of 60 years. Dr. Reisz and her colleagues observed statistical significance between cases and controls in terms of polypharmacy (P = .011), attention-deficit/hyperactivity disorder medications (P < .001), selective serotonin reuptake inhibitors (P = .005), opioids (P = .003), and gabapentin (P = .003).
In other findings, half of DOP cases presented with samples of perceived parasitic material, and four associated the perceived infestation with a single emotion-laden event. This prompted the researchers “to consider that DOP may share mechanisms with fear conditioning and extinction,” they wrote. “Fear conditioning refers to the process of memory acquisition and extinction. This process is essential for survival and has been studied in posttraumatic stress disorder.”
They acknowledged certain limitations of the study, including its retrospective single-center design and the lack of control for factors such as socioeconomic background and level of education.
“Patients with DOP should undergo detailed drug histories and examination of clearance profiles, especially renal function,” the researchers concluded.
Evan A. Rieder, MD, a New York City–based dermatologist and psychiatrist who was asked to comment on the study, said that delusional infestation is one of the most difficult medical conditions to treat and study.
“Though the numbers of cases in this research letter are small, they are instructive in demonstrating a high burden of polypharmacy including psychostimulants, opioids, and SSRIs in such patients,” he told this news organization. “Dermatologists should be performing detailed drug histories, obtaining comprehensive lab work, and considering the effects of medications — both illicit and prescribed — on clinical presentations. While in many cases, delusional patients refuse to consent to psychopharmacologic medications (or treatment in general), the elimination or decrease in dose of certain problematic medications may be helpful in and of themselves.”
The researchers reported having no financial disclosures. Dr. Rieder disclosed that he is a consultant for AbbVie, L’Oréal, Pierre Fabre, Procter & Gamble, and Unilever.
FROM THE JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
Lower olanzapine dose just as effective for chemotherapy-induced nausea, vomiting
SAN ANTONIO —
Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.
She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.
“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.
Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.
She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.
Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.
Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.
The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).
There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.
For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.
There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).
Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).
The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).
Low-dose patients also reported less appetite suppression.
The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.
SAN ANTONIO —
Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.
She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.
“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.
Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.
She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.
Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.
Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.
The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).
There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.
For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.
There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).
Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).
The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).
Low-dose patients also reported less appetite suppression.
The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.
SAN ANTONIO —
Although it’s highly effective in combination with standard antiemetic therapy, olanzapine at the standard dose of 10 mg makes people too drowsy. “This has prevented its widespread use in clinical practice,” medical oncologist Jyoti Bajpai, DM, of Tata Memorial Cancer Centre, Mumbai, India, explained at the San Antonio Breast Cancer Symposium.
She and her colleagues had a simple idea: Reduce the dose to 2.5 mg instead of 10 mg to prevent the problem. In a randomized trial with 267 patients that Dr. Bajpai presented at the meeting, they found that the lower dose was just as effective for nausea and vomiting prophylaxis, and it greatly reduced daytime somnolence.
“This merits consideration as an antiemetic regimen of choice for highly emetogenic chemotherapy.” The findings are “practice changing,” Dr. Bajpai, the lead investigator, said.
Laura Huppert, MD, a breast oncologist at the University of California, San Francisco, wasn’t surprised by the finding.
She said she and her colleagues at UCSF use a lot of olanzapine for nausea and vomiting prophylaxis. Like the team in India, they have found that 2.5 mg is effective and causes far less sleepiness. Some patients require 5 mg, but the full 10-mg dose is rarely needed.
Although the approach is familiar at UCSF, Dr. Huppert said she doesn’t think a lot of oncologists outside of academic centers know that olanzapine is “really helpful” and that “you don’t need a high dose.” It’s “a very good clinical pearl” and “definitely a new message for some,” she said in an interview.
Over 90% of the subjects in the study were women with breast cancer. Other cancers included sarcoma, germ cell tumors, and head and neck cancer. Subjects were scheduled for their first chemotherapy session with anthracycline-cyclophosphamide and high-dose cisplatin.
The trial randomized 135 patients to 10 mg of olanzapine and 132 to 2.5mg for 5 days, starting the day of their session. They were also on standard triple-antiemetic therapy (selective serotonin receptor (5-HT3) antagonist, neurokinin-1 receptor antagonist, and single-dose dexamethasone).
There were no significant differences between the two arms regarding nausea and vomiting, which patients tracked in daily journals using symptom severity and visual analog scales.
For instance, 44.7% in the 2.5-mg arm and 43.7% in the 10-mg arm reported no vomiting, no use of rescue medications, and no or only mild nausea (P = .87). Results were similar in the first 24 hours as well as on subsequent days.
There was also no difference in the proportion of patients who did have an emetic episode or needed rescue medication: 49.2% in the 2.5-mg arm versus 48.9% with 10 mg (P = .954).
Where the two groups split was on the incidence of daytime somnolence, which was reported by 65.2% of patients in the low-dose arm but 89.6% in the standard-dose group (P < .001). During the first 24 hours, 4.5% of low-dose patients reported severe somnolence versus 40% with 10-mg dosing (P < .001).
The overall incidence declined over the remaining study days, but the differences between the two groups were comparable. On day 5, for instance, 0.8% of low-dose patients but 8.1% of standard-dose patients reported severe somnolence (P = .004).
Low-dose patients also reported less appetite suppression.
The work was supported by the Progressive Ladies Welfare Association. Dr. Bajpai didn’t have any disclosures. Dr. Huppert is an adviser for AstraZeneca.
AT SABCS 2023
Should BP Guidelines Be Sex-Specific?
This transcript has been edited for clarity.
This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. Current BP guidelines are sex-agnostic.
This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.
Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.
In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.
Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.
If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. Current BP guidelines are sex-agnostic.
This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.
Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.
In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.
Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.
If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
This transcript has been edited for clarity.
This is Dr. JoAnn Manson, professor of medicine at Harvard Medical School and Brigham and Women’s Hospital. Current BP guidelines are sex-agnostic.
This study was done in the large-scale nationally representative NHANES cohort. It included more than 53,000 US men and women. The average age was about 45 years, with an average duration of follow-up of 9.5 years. During that time, about 2400 cardiovascular (CVD) deaths were documented at baseline. The BP was measured three times, and the results were averaged. About 20% of the cohort were taking antihypertensive medications, and 80% were not.
Sex differences were observed in the association between BP and CVD mortality. The systolic BP associated with the lowest risk for CVD death was 110-119 mm Hg in men and 100-109 mm Hg in women. In men, however, compared with a reference category of systolic BP of 100-109 mm Hg, the risk for CVD death began to increase significantly at a systolic BP ≥ 160 mm Hg, at which point, the hazard ratio was 1.76, or 76% higher risk.
In women, the risk for CVD death began to increase significantly at a lower threshold. Compared with a reference category of systolic BP of 100-109 mm Hg, women whose systolic BP was 130-139 mm Hg had a significant 61% increase in CVD death, and among those with a systolic BP of 140-159 mm Hg, the risk was increased by 75%. With a systolic BP ≥ 160 mm Hg, CVD deaths among women were more than doubled, with a hazard ratio of 2.13.
Overall, these findings suggest sex differences, with women having an increased risk for CVD death beginning at a lower elevation of their systolic BP. For diastolic BP, both men and women showed the typical U-shaped curve and the diastolic BP associated with the lowest risk for CVD death was 70-80 mm Hg.
If these findings can be replicated with additional research and other large-scale cohort studies, and randomized trials show differences in lowering BP, then sex-specific BP guidelines could have advantages and should be seriously considered. Furthermore, some of the CVD risk scores and risk modeling should perhaps use sex-specific blood pressure thresholds.Dr. Manson received study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).
A version of this article appeared on Medscape.com.
Where Is the ‘Microbiome Revolution’ Headed Next?
Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.
, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.
Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.
In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.
Highlighting the Most Promising Applications
Which recent studies on the link between the human microbiome and disease have you found particularly promising?
There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia.
Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research.
What other disease states may be amenable to microbiome-based interventions?
There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions.
It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases.
It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent Clostridioides difficile infections. What do you see as the next disease states where FMT could prove successful?
If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases.
Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness.
The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?
There is an emerging science about this question, driven in part by classical ecological theory.
Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure.
Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?
The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier.
Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes.
For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses.
Predicting the Next Stages of the ‘Microbiome Revolution’
Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?
The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected.
Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?
Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years.
How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?
This is a very important and active area in clinical investigation, which needs to be ramped up.
Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future.
How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?
All are important, but unlike genetics, the microbiome is tractable, like diet and exercise.
It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible.
In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?
Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine.
Lessons From Decades at the Forefront
You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?
From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010.
The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness.
Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?
The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry.
A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?
People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health.
The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs.
Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?
The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy.
The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance.
A version of this article appeared on Medscape.com.
Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.
, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.
Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.
In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.
Highlighting the Most Promising Applications
Which recent studies on the link between the human microbiome and disease have you found particularly promising?
There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia.
Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research.
What other disease states may be amenable to microbiome-based interventions?
There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions.
It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases.
It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent Clostridioides difficile infections. What do you see as the next disease states where FMT could prove successful?
If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases.
Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness.
The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?
There is an emerging science about this question, driven in part by classical ecological theory.
Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure.
Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?
The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier.
Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes.
For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses.
Predicting the Next Stages of the ‘Microbiome Revolution’
Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?
The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected.
Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?
Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years.
How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?
This is a very important and active area in clinical investigation, which needs to be ramped up.
Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future.
How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?
All are important, but unlike genetics, the microbiome is tractable, like diet and exercise.
It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible.
In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?
Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine.
Lessons From Decades at the Forefront
You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?
From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010.
The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness.
Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?
The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry.
A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?
People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health.
The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs.
Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?
The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy.
The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance.
A version of this article appeared on Medscape.com.
Human microbiome research has progressed in leaps and bounds over the past decades, from pivotal studies begun in the 1970s to the launch of the Human Microbiome Project in 2007. Breakthroughs have laid the groundwork for more recent clinical applications, such as fecal microbiota transplantation (FMT), and advanced techniques to explore new therapeutic pathways. Yet the “microbiome revolution” is just getting started, according to professor Martin J. Blaser, MD, one of the field’s pioneers.
, says Dr. Blaser, who holds the Henry Rutgers Chair of the Human Microbiome and is director of the Center for Advanced Biotechnology and Medicine at Rutgers University in New Brunswick, New Jersey.
Dr. Blaser is the author of Missing Microbes: How the Overuse of Antibiotics Is Fueling Our Modern Plagues, serves as chair of the Presidential Advisory Council on Combating Antibiotic-Resistant Bacteria and is a member of the scientific advisory board of the biotech startup Micronoma.
In this interview, which has been condensed and edited for clarity, Dr. Blaser discusses where we’re at now and where he sees the microbiome field evolving in the coming years.
Highlighting the Most Promising Applications
Which recent studies on the link between the human microbiome and disease have you found particularly promising?
There have been a number of studies, including our own, focusing on the gut-kidney axis. The gut microbiome produces, or detoxifies, metabolites that are toxic to the kidney: for example, those involved in the formation of kidney stones and in the worsening of uremia.
Altering the microbiome to reduce the uremic toxins and the nidus for stone formation is a very promising field of research.
What other disease states may be amenable to microbiome-based interventions?
There are diseases that are caused by known genetic mutations. Yet, for nearly all of them, there is great variation in clinical outcomes, which might be classed as genes multiplied by environment interactions.
It seems likely to me that microbiome variation could account for some proportion of those differences for some genetic diseases.
It’s now well established that altering the microbiome with FMT is a successful intervention for recurrent Clostridioides difficile infections. What do you see as the next disease states where FMT could prove successful?
If you go to ClinicalTrials.gov, you will find that that there are 471 trials registered using FMT. This is across a broad range of illnesses, including metabolic, immunological, autoimmune, inflammatory, degenerative, and neoplastic diseases.
Which will be the next condition showing marked efficacy is anyone’s guess. That is why we must do clinical trials to assess what works and what does not, regardless of specific illness.
The donor’s microbiome appears to be vital to engraftment success, with “superdonors” even being identified. What factors do you think primarily influence microbiome engraftment?
There is an emerging science about this question, driven in part by classical ecological theory.
Right now, we are using FMT as if one size fits all. But this probably would not provide optimal treatment for all. Just as we type blood donors and recipients before the blood transfusion, one could easily imagine a parallel kind of procedure.
Are there any diseases where it’s just too far-fetched to think altering the microbiome could make a difference?
The link between the microbiome and human health is so pervasive that there are few conditions that are out of the realm of possibility. It really is a frontier.
Not that the microbiome causes everything, but by understanding and manipulating the microbiome, we could at least palliate, or slow down, particular pathologic processes.
For all the major causes of death in the United States — cardiovascular disease, cancer, dementia and neurogenerative diseases, diabetes, and lung, liver, and kidney diseases — there is ongoing investigation of the microbiome. A greater promise would be to prevent or cure these illnesses.
Predicting the Next Stages of the ‘Microbiome Revolution’
Do you believe we are at a turning point with the microbiome in terms of being able to manipulate or engineer it?
The microbiome is a scientific frontier that has an impact across the biosphere. It is a broad frontier involving human and veterinary medicine, agriculture, and the environment. Knowledge is increasing incrementally, as expected.
Are we at the point yet where doctors should be incorporating microbiome-related lifestyle changes for people with or at risk for cancer, heart disease, Alzheimer’s disease, or other chronic conditions?
Although we are still in the early stages of the “microbiome revolution,” which I first wrote about in EMBO Reports in 2006 and then again in the Journal of Clinical Investigation in 2014, I think important advances for all of these conditions are coming our way in the next 5-10 years.
How are prebiotics, probiotics, and postbiotics being used to shape the microbiome?
This is a very important and active area in clinical investigation, which needs to be ramped up.
Tens of millions of people are using probiotics and prebiotics every day for vague indications, and which have only infrequently been tested in robust clinical trials. So, there is a disconnect between what’s being claimed with the bulk of the probiotics at present and what we’ll actually know in the future.
How do you think the microbiome will stack up to other factors influencing health, such as genetics, exercise, and nutrition?
All are important, but unlike genetics, the microbiome is tractable, like diet and exercise.
It is essentially impossible to change one’s genome, but that might become more likely before too long. However, we can easily change someone’s microbiome through dietary means, for example. Once we know the ground rules, there will be many options. Right now, it is mostly one-offs, but as the scientific basis broadens, much more will be possible.
In the future, do you think we’ll be able to look at a person’s microbiome and tell what his or her risk of developing disease is, similar to the way we use gene panels now?
Yes, but we will need scientific advances to teach us what are the important biomarkers in general and in particular people. This will be one area of precision medicine.
Lessons From Decades at the Forefront
You’ve been involved in this research for over 30 years, and the majority has focused on the human microbiome and its role in disease. When did it become apparent to you that this research had unique therapeutic promise?
From the very start, there was always the potential to harness the microbiome to improve human health. In fact, I wrote a perspective in PNAS on that theme in 2010.
The key is to understand the biology of the microbiome, and from the scientific study comes new preventives and new treatments. Right now, there are many “probiotic” products on the market. Probiotics have a great future, but most of what is out there has not been rigorously tested for effectiveness.
Was there a particular series of studies that occurred before the launch of the Human Microbiome Project and brought us to the current era?
The studies in the 1970s-1980s by Carl Woese using 16S rRNA genes to understand phylogeny and evolution opened up the field of DNA sequencing to consider bacterial evolution and issues of ancestry.
A key subject of your research and the focus of your book is antibiotic-resistant bacteria. What did this work teach you about describing the science of antibiotic resistance to the general public?
People don’t care very much about antibiotic resistance. They think that affects other people, mostly. In contrast, they care about their own health and their children’s health.
The more that the data show that using antibiotics can be harmful to health in some circumstances, the more that use will diminish. We need more transparency about benefits and costs.
Are there any common misconceptions about the microbiome that you hear from the general public, or even clinicians, that you would like to see greater efforts to dispel?
The public and the medical profession are in love with probiotics, buying them by the tens of millions. But as stated before, they are very diverse and mostly untested for efficacy.
The next step is to test specific formulations to see which ones work, and for whom, and which ones don’t. That would be a big advance.
A version of this article appeared on Medscape.com.
Roflumilast foam gets nod as new option for seborrheic dermatitis
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
The in a press release.
The 0.3% foam, marketed as Zoryve, applied once-daily, is indicated for patients aged 9 years and older with seborrheic dermatitis, and can be used anywhere on the body, including areas with hair, with no limits on duration of use, according to the company, Arcutis. A 0.3% cream formulation of roflumilast was previously approved by the FDA for the topical treatment of plaque psoriasis in patients aged 6 years and older.
Approval was based on data from the phase 3 STRATUM trial and an accompanying phase 2 study known as Trial 203. These studies included a total of 683 adults and youth aged 9 years and older with seborrheic dermatitis. Participants were randomized to roflumilast or a placebo.
At 8 weeks, 79.5 % of patients on roflumilast met the primary efficacy endpoint of Investigator Global Assessment (IGA) scores of 0 or 1 (clear or almost clear) compared with 58.0% of patients on placebo (P < .001); the results were similar in the phase 2 Trial 203 (73.1% vs. 40.8%, respectively; P < .001). Overall, more than 50% of the patients on roflumilast achieved a clear score.
Patients in the roflumilast group also showed significant improvement in all secondary endpoints, including itching, scaling, and erythema, according to the company.
In the STRATUM study, 62.8% of roflumilast-treated patients and 40.6% of placebo patients achieved a 4-point or more reduction in itch based on the Worst Itch Numerical Rating Score (P =.0001), and 28% of roflumilast-treated patients reported significant itch improvement within the first 48 hours of use, compared with 13% of placebo patients (P = .0024).
Over a treatment period of up to 1 year, no treatment-related severe adverse events were reported in the phase 2 and 3 studies. The incidence of treatment emergent adverse events was similar between the treatment and placebo groups, and the most common adverse events (occurring in 1% of more of patients) across both studies were nasopharyngitis (1.5%), nausea (1.3%), and headache (1.1%).
Roflumilast foam is scheduled to be available by the end of January 2024, according to the company. The product is for topical use only, and contraindicated for individuals with severe liver impairment.
What causes obesity? More science points to the brain
For much of his life, 32-year-old Michael Smith had a war going on in his head.
After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again.
Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.
He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control.
“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “
Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results.
Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.
But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise.
But most agree that in the battle against obesity, one crucial organ has been overlooked.
“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”
A Break in the Machine
Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.
said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”
Mounting evidence suggests that in people with obesity, something in the machine is broken.
One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack.
A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.
“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.
Gut-brain pathways that tell us we’re full may also be impaired.
In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).
In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).
In those with obesity, the brain barely responded at all.
“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”
Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.
“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.
Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.
The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.
“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”
In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.
All this raises a crucial question: How do these circuits and pathways malfunction in the first place?
What Breaks the Brain?
Genes, scientists agree, play a role.
Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments.
While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.
Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.
At the population level, “our genes don’t change that much in less than a generation,” she said.
But our food supply has.
Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.
“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias.
In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food.
The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.
Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.
“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall.
Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else.
Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full.
“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science.
Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.
And once these brain changes are made, they are hard to reverse.
“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”
That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.
A New Era of Brain-Based Solutions
In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.
“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.
A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses.
While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.
His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full.
The weight began to fall off again.
Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.
“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’”
A Multi-Pronged Approach
Dr. Halpern, at Penn, has also been hearing success stories.
In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder.
All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.
The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.
Thus far, all three are seeing promising results.
“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”
Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.
He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.
Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.
“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.
Still, not everyone believes brain-based drugs and surgeries are the answer.
David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.
He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.
“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.”
Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.
“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”
Smith says understanding this has been a big part of his success.
He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.
Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.
“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
A version of this article appeared on WebMD.com .
For much of his life, 32-year-old Michael Smith had a war going on in his head.
After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again.
Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.
He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control.
“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “
Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results.
Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.
But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise.
But most agree that in the battle against obesity, one crucial organ has been overlooked.
“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”
A Break in the Machine
Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.
said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”
Mounting evidence suggests that in people with obesity, something in the machine is broken.
One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack.
A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.
“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.
Gut-brain pathways that tell us we’re full may also be impaired.
In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).
In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).
In those with obesity, the brain barely responded at all.
“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”
Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.
“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.
Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.
The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.
“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”
In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.
All this raises a crucial question: How do these circuits and pathways malfunction in the first place?
What Breaks the Brain?
Genes, scientists agree, play a role.
Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments.
While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.
Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.
At the population level, “our genes don’t change that much in less than a generation,” she said.
But our food supply has.
Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.
“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias.
In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food.
The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.
Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.
“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall.
Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else.
Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full.
“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science.
Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.
And once these brain changes are made, they are hard to reverse.
“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”
That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.
A New Era of Brain-Based Solutions
In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.
“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.
A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses.
While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.
His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full.
The weight began to fall off again.
Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.
“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’”
A Multi-Pronged Approach
Dr. Halpern, at Penn, has also been hearing success stories.
In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder.
All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.
The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.
Thus far, all three are seeing promising results.
“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”
Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.
He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.
Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.
“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.
Still, not everyone believes brain-based drugs and surgeries are the answer.
David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.
He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.
“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.”
Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.
“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”
Smith says understanding this has been a big part of his success.
He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.
Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.
“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
A version of this article appeared on WebMD.com .
For much of his life, 32-year-old Michael Smith had a war going on in his head.
After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again.
Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.
He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control.
“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “
Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results.
Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.
But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise.
But most agree that in the battle against obesity, one crucial organ has been overlooked.
“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”
A Break in the Machine
Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.
said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”
Mounting evidence suggests that in people with obesity, something in the machine is broken.
One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack.
A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.
“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.
Gut-brain pathways that tell us we’re full may also be impaired.
In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).
In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).
In those with obesity, the brain barely responded at all.
“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”
Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.
“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.
Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.
The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.
“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”
In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.
All this raises a crucial question: How do these circuits and pathways malfunction in the first place?
What Breaks the Brain?
Genes, scientists agree, play a role.
Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments.
While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.
Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.
At the population level, “our genes don’t change that much in less than a generation,” she said.
But our food supply has.
Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.
“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias.
In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food.
The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.
Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.
“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall.
Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else.
Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full.
“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science.
Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.
And once these brain changes are made, they are hard to reverse.
“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”
That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.
A New Era of Brain-Based Solutions
In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.
“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.
A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses.
While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.
His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full.
The weight began to fall off again.
Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.
“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’”
A Multi-Pronged Approach
Dr. Halpern, at Penn, has also been hearing success stories.
In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder.
All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.
The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.
Thus far, all three are seeing promising results.
“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”
Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.
He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.
Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.
“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.
Still, not everyone believes brain-based drugs and surgeries are the answer.
David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.
He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.
“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.”
Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.
“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”
Smith says understanding this has been a big part of his success.
He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.
Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.
“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
A version of this article appeared on WebMD.com .
FDA approves implant for glaucoma
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
The iDose TR (Glaukos Corp) is inserted into a corneal incision on the temple side of the eye. Pivotal phase 3 clinical trials showed the treatment resulted in sustained reductions in IOP for 3 months ranging from 6.6 to 8.4 mm Hg, comparable to reductions with topical timolol 0.5% drops used twice daily. Normal IOP is 10-21 mm Hg, and glaucoma treatments are designed to reduce high IOP into the normal range.
Glaukos Corp said that it intends a commercial launch of the implant early in 2024, with a wholesale cost of $13,950 per implant.
Travoprost is a prostaglandin analog that has been long used as a topical formulation for lowering IOP in OAG and OHT. Timolol is a topical beta-blocker widely used for the same indications.
iDose TR comes in a preloaded handheld injector designed to deliver the implant into the sclera of the eye. The implant seats in the junction of the iris, sclera, and cornea.
In two phase 3 clinical trials, 81% of patients who received the iDose TR did not require supplemental drops to reduce IOP after 12 months compared with 95% of those who receive timolol alone.
The phase 3 trials included 1150 participants across 89 clinical sites. Both trials, GC-010 and GC-012, met the primary endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months, according to results that John Berdahl, MD, a researcher with Vance Thompson Vision in Sioux Falls, South Dakota, and an investigator for Glaukos, presented in May at the annual meeting of the American Society of Cataract and Refractive Surgery.
Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated noninferiority to topical timolol in reduction of IOP during the first 3 months of treatment. The agency also noted that use of iDose TR did not demonstrate noninferiority over the next 9 months.
In the controlled studies, the most common ocular adverse reactions reported in 2% to 6% of patients who received iDose TR were increases in IOP , iritis, dry eye, and defects of the visual field, most of which were said to be mild and transient in nature.
A version of this article appeared on Medscape.com.
GVHD raises vitiligo risk in transplant recipients
published online in JAMA Dermatology December 13.
In the cohort study, the greatest risk occurred with hematopoietic stem cell transplants (HSCTs) and in cases involving GVHD. Kidney and liver transplants carried slight increases in risk.
“The findings suggest that early detection and management of vitiligo lesions can be improved by estimating the likelihood of its development in transplant recipients and implementing a multidisciplinary approach for monitoring,” wrote the authors, from the departments of dermatology and biostatistics, at the Catholic University of Korea, Seoul.
Using claims data from South Korea’s National Health Insurance Service database, the investigators compared vitiligo incidence among 23,829 patients who had undergone solid organ transplantation (SOT) or HSCT between 2010 and 2017 versus that of 119,145 age- and sex-matched controls. At a mean observation time of 4.79 years in the transplant group (and 5.12 years for controls), the adjusted hazard ratio (AHR) for vitiligo among patients who had undergone any transplant was 1.73. AHRs for HSCT, liver transplants, and kidney transplants were 12.69, 1.63, and 1.50, respectively.
Patients who had undergone allogeneic HSCT (AHR, 14.43) or autologous transplants (AHR, 5.71), as well as those with and without GVHD (24.09 and 8.21, respectively) had significantly higher vitiligo risk than the control group.
Among those with GVHD, HSCT recipients (AHR, 16.42) and those with allogeneic grafts (AHR, 16.81) had a higher vitiligo risk than that of control patients.
In a subgroup that included 10,355 transplant recipients who underwent posttransplant health checkups, investigators found the highest vitiligo risk — AHR, 25.09 versus controls — among HSCT recipients with comorbid GVHD. However, patients who underwent SOT, autologous HSCT, or HSCT without GVHD showed no increased vitiligo risk in this analysis. “The results of health checkup data analysis may differ from the initial analysis due to additional adjustments for lifestyle factors and inclusion of only patients who underwent a health checkup,” the authors wrote.
Asked to comment on the results, George Han, MD, PhD, who was not involved with the study, told this news organization, “this is an interesting paper where the primary difference from previous studies is the new association between GVHD in hematopoietic stem cell transplant recipients and vitiligo.” Prior research had shown higher rates of vitiligo in HSCT recipients without making the GVHD distinction. Dr. Han is associate professor of dermatology in the Hofstra/Northwell Department of Dermatology, Hyde Park, New York.
Although GVHD may not be top-of-mind for dermatologists in daily practice, he said, the study enhances their understanding of vitiligo risk in HSCT recipients. “In some ways,” Dr. Han added, “the association makes sense, as the activated T cells from the graft attacking the skin in the HSCT recipient follow many of the mechanisms of vitiligo, including upregulating interferon gamma and the CXCR3/CXCL10 axis.”
Presently, he said, dermatologists worry more about solid organ recipients than about HSCT recipients because the long-term immunosuppression required by SOT increases the risk of squamous cell carcinoma (SCC). “However, the risk of skin cancers also seems to be elevated in HSCT recipients, and in this case the basal cell carcinoma (BCC):SCC ratio is not necessarily reversed as we see in solid organ transplant recipients. So the mechanisms are a bit less clear. Interestingly, acute and chronic GVHD have both been associated with increased risks of BCC and SCC/BCC, respectively.”
Overall, Dr. Han said, any transplant recipient should undergo yearly skin checks not only for skin cancers, but also for other skin conditions such as vitiligo. “It would be nice to see this codified into official guidelines, which can vary considerably but are overall more consistent in solid organ transplant recipients than in HSCT recipients. No such guidelines seem to be available for HSCTs.”
The study was funded by the Basic Research in Science & Engineering program through the National Research Foundation of Korea, which is funded by the country’s Ministry of Education. The study authors had no disclosures. Dr. Han reports no relevant financial interests.
published online in JAMA Dermatology December 13.
In the cohort study, the greatest risk occurred with hematopoietic stem cell transplants (HSCTs) and in cases involving GVHD. Kidney and liver transplants carried slight increases in risk.
“The findings suggest that early detection and management of vitiligo lesions can be improved by estimating the likelihood of its development in transplant recipients and implementing a multidisciplinary approach for monitoring,” wrote the authors, from the departments of dermatology and biostatistics, at the Catholic University of Korea, Seoul.
Using claims data from South Korea’s National Health Insurance Service database, the investigators compared vitiligo incidence among 23,829 patients who had undergone solid organ transplantation (SOT) or HSCT between 2010 and 2017 versus that of 119,145 age- and sex-matched controls. At a mean observation time of 4.79 years in the transplant group (and 5.12 years for controls), the adjusted hazard ratio (AHR) for vitiligo among patients who had undergone any transplant was 1.73. AHRs for HSCT, liver transplants, and kidney transplants were 12.69, 1.63, and 1.50, respectively.
Patients who had undergone allogeneic HSCT (AHR, 14.43) or autologous transplants (AHR, 5.71), as well as those with and without GVHD (24.09 and 8.21, respectively) had significantly higher vitiligo risk than the control group.
Among those with GVHD, HSCT recipients (AHR, 16.42) and those with allogeneic grafts (AHR, 16.81) had a higher vitiligo risk than that of control patients.
In a subgroup that included 10,355 transplant recipients who underwent posttransplant health checkups, investigators found the highest vitiligo risk — AHR, 25.09 versus controls — among HSCT recipients with comorbid GVHD. However, patients who underwent SOT, autologous HSCT, or HSCT without GVHD showed no increased vitiligo risk in this analysis. “The results of health checkup data analysis may differ from the initial analysis due to additional adjustments for lifestyle factors and inclusion of only patients who underwent a health checkup,” the authors wrote.
Asked to comment on the results, George Han, MD, PhD, who was not involved with the study, told this news organization, “this is an interesting paper where the primary difference from previous studies is the new association between GVHD in hematopoietic stem cell transplant recipients and vitiligo.” Prior research had shown higher rates of vitiligo in HSCT recipients without making the GVHD distinction. Dr. Han is associate professor of dermatology in the Hofstra/Northwell Department of Dermatology, Hyde Park, New York.
Although GVHD may not be top-of-mind for dermatologists in daily practice, he said, the study enhances their understanding of vitiligo risk in HSCT recipients. “In some ways,” Dr. Han added, “the association makes sense, as the activated T cells from the graft attacking the skin in the HSCT recipient follow many of the mechanisms of vitiligo, including upregulating interferon gamma and the CXCR3/CXCL10 axis.”
Presently, he said, dermatologists worry more about solid organ recipients than about HSCT recipients because the long-term immunosuppression required by SOT increases the risk of squamous cell carcinoma (SCC). “However, the risk of skin cancers also seems to be elevated in HSCT recipients, and in this case the basal cell carcinoma (BCC):SCC ratio is not necessarily reversed as we see in solid organ transplant recipients. So the mechanisms are a bit less clear. Interestingly, acute and chronic GVHD have both been associated with increased risks of BCC and SCC/BCC, respectively.”
Overall, Dr. Han said, any transplant recipient should undergo yearly skin checks not only for skin cancers, but also for other skin conditions such as vitiligo. “It would be nice to see this codified into official guidelines, which can vary considerably but are overall more consistent in solid organ transplant recipients than in HSCT recipients. No such guidelines seem to be available for HSCTs.”
The study was funded by the Basic Research in Science & Engineering program through the National Research Foundation of Korea, which is funded by the country’s Ministry of Education. The study authors had no disclosures. Dr. Han reports no relevant financial interests.
published online in JAMA Dermatology December 13.
In the cohort study, the greatest risk occurred with hematopoietic stem cell transplants (HSCTs) and in cases involving GVHD. Kidney and liver transplants carried slight increases in risk.
“The findings suggest that early detection and management of vitiligo lesions can be improved by estimating the likelihood of its development in transplant recipients and implementing a multidisciplinary approach for monitoring,” wrote the authors, from the departments of dermatology and biostatistics, at the Catholic University of Korea, Seoul.
Using claims data from South Korea’s National Health Insurance Service database, the investigators compared vitiligo incidence among 23,829 patients who had undergone solid organ transplantation (SOT) or HSCT between 2010 and 2017 versus that of 119,145 age- and sex-matched controls. At a mean observation time of 4.79 years in the transplant group (and 5.12 years for controls), the adjusted hazard ratio (AHR) for vitiligo among patients who had undergone any transplant was 1.73. AHRs for HSCT, liver transplants, and kidney transplants were 12.69, 1.63, and 1.50, respectively.
Patients who had undergone allogeneic HSCT (AHR, 14.43) or autologous transplants (AHR, 5.71), as well as those with and without GVHD (24.09 and 8.21, respectively) had significantly higher vitiligo risk than the control group.
Among those with GVHD, HSCT recipients (AHR, 16.42) and those with allogeneic grafts (AHR, 16.81) had a higher vitiligo risk than that of control patients.
In a subgroup that included 10,355 transplant recipients who underwent posttransplant health checkups, investigators found the highest vitiligo risk — AHR, 25.09 versus controls — among HSCT recipients with comorbid GVHD. However, patients who underwent SOT, autologous HSCT, or HSCT without GVHD showed no increased vitiligo risk in this analysis. “The results of health checkup data analysis may differ from the initial analysis due to additional adjustments for lifestyle factors and inclusion of only patients who underwent a health checkup,” the authors wrote.
Asked to comment on the results, George Han, MD, PhD, who was not involved with the study, told this news organization, “this is an interesting paper where the primary difference from previous studies is the new association between GVHD in hematopoietic stem cell transplant recipients and vitiligo.” Prior research had shown higher rates of vitiligo in HSCT recipients without making the GVHD distinction. Dr. Han is associate professor of dermatology in the Hofstra/Northwell Department of Dermatology, Hyde Park, New York.
Although GVHD may not be top-of-mind for dermatologists in daily practice, he said, the study enhances their understanding of vitiligo risk in HSCT recipients. “In some ways,” Dr. Han added, “the association makes sense, as the activated T cells from the graft attacking the skin in the HSCT recipient follow many of the mechanisms of vitiligo, including upregulating interferon gamma and the CXCR3/CXCL10 axis.”
Presently, he said, dermatologists worry more about solid organ recipients than about HSCT recipients because the long-term immunosuppression required by SOT increases the risk of squamous cell carcinoma (SCC). “However, the risk of skin cancers also seems to be elevated in HSCT recipients, and in this case the basal cell carcinoma (BCC):SCC ratio is not necessarily reversed as we see in solid organ transplant recipients. So the mechanisms are a bit less clear. Interestingly, acute and chronic GVHD have both been associated with increased risks of BCC and SCC/BCC, respectively.”
Overall, Dr. Han said, any transplant recipient should undergo yearly skin checks not only for skin cancers, but also for other skin conditions such as vitiligo. “It would be nice to see this codified into official guidelines, which can vary considerably but are overall more consistent in solid organ transplant recipients than in HSCT recipients. No such guidelines seem to be available for HSCTs.”
The study was funded by the Basic Research in Science & Engineering program through the National Research Foundation of Korea, which is funded by the country’s Ministry of Education. The study authors had no disclosures. Dr. Han reports no relevant financial interests.
FROM JAMA DERMATOLOGY