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Some, not all, ultraprocessed foods linked to type 2 diabetes
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
High total intake of ultraprocessed food (UPF) is associated with an increased risk of developing type 2 diabetes, suggests a large-scale analysis that nevertheless revealed that the risk applies only to certain such foods.
The research was recently published in Diabetes Care by Zhangling Chen, PhD, Erasmus MC Rotterdam, Netherlands, and colleagues.
Examining almost 200,000 participants in three U.S. studies, yielding more than 5 million person-years of follow-up, the scientists found that high intake of UPF was associated with a 28% increased risk of type 2 diabetes, after statistical adjustments.
However, the increased risk was restricted to certain UPFs, including ready meals, refined breads, sweetened beverages, and sauces and condiments, with other foods considered UPFs, such as cereals, dark- and whole grain breads, and packaged sweet and savory snacks, among others, associated with a reduced risk of diabetes.
Senior author Jean-Philippe Drouin-Chartier, PhD, Nutrition Center, Laval University, Quebec City, told this news organization: “While whole grain breads can be considered as ultraprocessed foods, their consumption should not be discouraged. In our study, we observed that whole grain breads consumption is inversely associated with type 2 diabetes risk. This is supported by many studies linking dietary fiber consumption to better cardiometabolic health.”
Ultraprocessed food intake higher in the U.S. than in Europe
The researchers note that a handful of European studies have also reported an association between UPF consumption and increased type 2 diabetes risk, with the effect ranging from 15% to 53%, depending on the level of intake and the cohort of patients studied.
They note, however, that total UPF intake in the U.S. is “much higher than in Europe,” particularly in the case of ultraprocessed breads and cereals and artificially or sugar-sweetened beverages.
In the current study, they examined data on 71,781 women from the Nurses’ Health Study, 87,918 women from the NHS II, and 38,847 men from the Health Professional Follow-up Study, none of whom had cardiovascular disease, cancer, or diabetes at baseline.
In all three studies, questionnaires were administered every 2 years to collect demographic, lifestyle, and medical information, and a validated food frequency questionnaire was used every 2-4 years to assess participants’ diets over 30 years of follow-up.
Using the NOVA Food Classification system, the items on the food frequency questionnaire were categorized into one of four groups: unprocessed or minimally processed foods; processed culinary ingredients; processed foods; or UPFs, which were subdivided into nine mutually exclusive subgroups.
Servings per day were then used to determine individual UPF intake.
Higher total UPF intake was associated with a greater total energy intake, body mass index, and prevalence of hypercholesterolemia and/or hypertension, as well as lower healthy eating scores and physical activity.
The researchers calculated that, over 5,187,678 person-years of follow-up, there were 19,503 cases of type 2 diabetes across the three study cohorts.
Multivariate analysis taking into consideration a range of potential risk factors, including BMI, revealed that, across the three study cohorts, the highest quintile of UPF intake was associated with a significantly increased risk of type 2 diabetes.
Compared with the lowest quintile of UPF intake, the hazard ratio for incident type 2 diabetes was 1.28 (P < .0001), with an increase in risk per additional serving per day of 3%.
The UPFs associated with a higher type 2 diabetes risk were as previously described and also included animal-based products and ready-to-eat mixed dishes.
In contrast, intake of UPFs including cereals, dark and whole grain breads, packaged sweet and savory snacks, fruit-based products, and yogurt and dairy-based desserts were linked to a reduced risk of type 2 diabetes.
Then to further validate their findings, the researchers conducted a meta-analysis of their own and four additional studies, comprising 415,554 participants and 21,932 events, with a follow-up of 3.4-32.0 years.
They determined that the pooled relative risk of type 2 diabetes with the highest versus lowest levels of UPF consumption was 1.40, with each 10% increase in total UPF intake associated with a 12% increase in diabetes risk.
Ideal is to have access to minimally processed foods
The NOVA food classification system states that UPFs are industrial formulations “made mostly or entirely with substances extracted from foods, often chemically modified, with additives and with little, if any, whole foods added.”
A recent study questioned the value of the NOVA classification after finding that it had “low consistency” when assigning foods.
Previous studies have nevertheless revealed that UPFs and their constituents negatively affect the gut microbiota and can cause systemic inflammation, insulin resistance, and increased body weight.
Dr. Drouin-Chartier concluded: “There is a need to facilitate ... access to minimally processed foods. This encompasses [appropriate] pricing and physical access [to such foods], that is, addressing the issue of food deserts.”
The NHS I and II and HPFS studies are supported by National Institutes of Health. Dr. Drouin-Chartier has reported a relationship with the Dairy Farmers of Canada. No other financial relationships were declared.
A version of this article first appeared on Medscape.com.
FROM DIABETES CARE
TikTok’s fave weight loss drugs: Link to thyroid cancer?
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
With #Ozempic and #ozempicweightloss continuing to trend on social media, along with the mainstream media focusing on celebrities who rely on Ozempic (semaglutide) for weight loss, the daily requests for this new medication have been increasing.
Accompanying these requests are concerns and questions about potential risks, including this most recent message from one of my patients: “Dr. P – I saw the warnings. Is this medication going to make me get thyroid cancer? Please let me know!”
Let’s look at what we know to date, including recent studies, and how to advise our patients on this very hot topic.
Using GLP-1 receptor agonists for obesity
We have extensive prior experience with glucagon-like peptide 1 (GLP-1) receptor agonists, such as semaglutide, for treating type 2 diabetes and now recently as agents for weight loss.
Large clinical trials have documented the benefits of this medication class not only for weight reduction but also for cardiovascular and renal benefits in patients with diabetes. The subcutaneously injectable medications work by promoting insulin secretion, slowing gastric emptying, and suppressing glucagon secretion, with a low risk for hypoglycemia.
The Food and Drug Administration approved daily-injection GLP-1 agonist liraglutide for weight loss in 2014, and weekly-injection semaglutide for chronic weight management in 2021, in patients with a body mass index ≥ 27 with at least one weight-related condition or a BMI ≥ 30.
The brand name for semaglutide approved for weight loss is Wegovy, and the dose is slightly higher (maximum 2.4 mg/wk) than that of Ozempic (maximum 2.0 mg/wk), which is semaglutide approved for type 2 diabetes.
In trials for weight loss, data showed a mean change in body weight of almost 15% in the semaglutide group at week 68 compared with placebo, which is very impressive, particularly compared with other FDA-approved oral long-term weight loss medications.
The newest synthetic dual-acting agent is tirzepatide, which targets GLP-1 but is also a glucose-dependent insulinotropic polypeptide (GIP) agonist. The weekly subcutaneous injection was approved in May 2022 as Mounjaro for treating type 2 diabetes and produced even greater weight loss than semaglutide in clinical trials. Tirzepatide is now in trials for obesity and is under expedited review by the FDA for weight loss.
Why the concern about thyroid cancer?
Early on with the FDA approvals of GLP-1 agonists, a warning accompanied the products’ labels to not use this class of medications in patients with medullary thyroid cancer, a family history of medullary thyroid cancer, or multiple endocrine neoplasia syndrome type 2. This warning was based on data from animal studies.
Human pancreatic cells aren’t the only cells that express GLP-1 receptors. These receptors are also expressed by parafollicular cells (C cells) of the thyroid, which secrete calcitonin and are the cells involved in medullary thyroid cancer. A dose-related and duration-dependent increase in thyroid C-cell tumor incidence was noted in rodents. The same relationship was not demonstrated in monkeys. Humans have far fewer C cells than rats, and human C cells have very low expression of the GLP-1 receptor.
Over a decade ago, a study examining the FDA’s database of reported adverse events found an increased risk for thyroid cancer in patients treated with exenatide, another GLP-1 agonist. The reporting system wasn’t designed to distinguish thyroid cancer subtypes.
Numerous subsequent studies didn’t confirm this relationship. The LEADER trial looked at liraglutide in patients with type 2 diabetes and showed no effect of GLP-1 receptor activation on human serum calcitonin levels, C-cell proliferation, or C-cell malignancy. Similarly, a large meta-analysis in patients with type 2 diabetes didn’t find a statistically increased risk for thyroid cancer with liraglutide, and no thyroid malignancies were reported with exenatide.
Two U.S. administrative databases from commercial health plans (a retrospective cohort study and a nested case-control study) compared type 2 diabetes patients who were taking exenatide vs. other antidiabetic drugs and found that exenatide was not significantly associated with an increased risk for thyroid cancer.
And a recent meta-analysis of 45 trials showed no significant effects on the occurrence of thyroid cancer with GLP-1 receptor agonists. Of note, it did find an increased risk for overall thyroid disorders, although there was no clear statistically significant finding pointing to a specific thyroid disorder.
Differing from prior studies, a recent nationwide French health care system study provided newer data suggesting a moderate increased risk for thyroid cancer in a cohort of patients with type 2 diabetes who were taking GLP-1 agonists. The increase in relative risk was noted for all types of thyroid cancer in patients using GLP-1 receptor agonists for 1-3 years.
An accompanying commentary by Caroline A. Thompson, PhD, and Til Stürmer, MD, provides perspective on this study’s potential limitations. These include detection bias, as the study results focused only on the statistically significant data. Also discussed were limitations to the case-control design, issues with claims-based tumor type classification (unavailability of surgical pathology), and an inability to adjust for family history and obesity, which is a risk factor alone for thyroid cancer. There was also no adjustment for exposure to head/neck radiation.
While this study has important findings to consider, it deserves further investigation, with future studies linking data to tumor registry data before a change is made in clinical practice.
No clear relationship has been drawn between GLP-1 receptor agonists and thyroid cancer in humans. Numerous confounding factors limit the data. Studies generally don’t specify the type of thyroid cancer, and they lump medullary thyroid cancer, the rarest form, with papillary thyroid cancer.
Is a detection bias present where weight loss makes nodules more visible on the neck among those treated with GLP-1 agonists? And/or are patients treated with GLP-1 agonists being screened more stringently for thyroid nodules and/or cancer?
How to advise our patients and respond to the EMR messages
The TikTok videos may continue, the celebrity chatter may increase, and we, as physicians, will continue to look to real-world data with randomized controlled trials to tailor our decision-making and guide our patients.
Thyroid cancer remains a rare outcome, and GLP-1 receptor agonists remain a very important and beneficial treatment option for the right patient.
A version of this article first appeared on Medscape.com.
The human-looking robot therapist will coach your well-being now
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
Do android therapists dream of electric employees?
Robots. It can be tough to remember that, when they’re not dooming humanity to apocalypse or just telling you that you’re doomed, robots have real-world uses. There are actual robots in the world, and they can do things beyond bend girders, sing about science, or run the navy.
Look, we’ll stop with the pop-culture references when pop culture runs out of robots to reference. It may take a while.
Robots are indelibly rooted in the public consciousness, and that plays into our expectations when we encounter a real-life robot. This leads us into a recent study conducted by researchers at the University of Cambridge, who developed a robot-led mental well-being program that a tech company utilized for 4 weeks. Why choose a robot? Well, why spring for a qualified therapist who requires a salary when you could simply get a robot to do the job for free? Get with the capitalist agenda here. Surely it won’t backfire.
The 26 people enrolled in the study received coaching from one of two robots, both programmed identically to act like mental health coaches, based on interviews with human therapists. Both acted identically and had identical expressions. The only difference between the two was their appearance. QTRobot was nearly a meter tall and looked like a human child; Misty II was much smaller and looked like a toy.
People who received coaching from Misty II were better able to connect and had a better experience than those who received coaching from QTRobot. According to those in the QTRobot group, their expectations didn’t match reality. The robots are good coaches, but they don’t act human. This wasn’t a problem for Misty II, since it doesn’t look human, but for QTRobot, the participants were expecting “to hell with our orders,” but received “Daisy, Daisy, give me your answer do.” When you’ve been programmed to think of robots as metal humans, it can be off-putting to see them act as, well, robots.
That said, all participants found the exercises helpful and were open to receiving more robot-led therapy in the future. And while we’re sure the technology will advance to make robot therapists more empathetic and more human, hopefully scientists won’t go too far. We don’t need depressed robots.
Birthing experience is all in the mindset
Alexa, play Peer Gynt Suite No. 1, Op. 46 - I. Morning Mood.
Birth.
Giving birth is a common experience for many, if not most, female mammals, but wanting it to be a pleasurable one seems distinctly human. There are many methods and practices that may make giving birth an easier and enjoyable experience for the mother, but a new study suggests that the key could be in her mind.
The mindset of the expectant mother during pregnancy, it seems, has some effect on how smooth or intervention-filled delivery is. If the mothers saw their experience as a natural process, they were less likely to need pain medication or a C-section, but mothers who viewed the experience as more of a “medical procedure” were more likely to require more medical supervision and intervention, according to investigators from the University of Bonn (Germany).
Now, the researchers wanted to be super clear in saying that there’s no right or wrong mindset to have. They just focused on the outcomes of those mindsets and whether they actually do have some effect on occurrences.
Apparently, yes.
“Mindsets can be understood as a kind of mental lense that guide our perception of the world around us and can influence our behavior,” Dr. Lisa Hoffmann said in a statement from the university. “The study highlights the importance of psychological factors in childbirth.”
The researchers surveyed 300 women with an online tool before and after delivery and found the effects of the natural process mindset lingered even after giving birth. They had lower rates of depression and posttraumatic stress, which may have a snowballing effect on mother-child bonding after childbirth.
Preparation for the big day, then, should be about more than gathering diapers and shopping for car seats. Women should prepare their minds as well. If it’s going to make giving birth better, why not?
Becoming a parent is going to create a psychological shift, no matter how you slice it.
Giant inflatable colon reported in Utah
Do not be alarmed! Yes, there is a giant inflatable colon currently at large in the Beehive State, but it will not harm you. The giant inflatable colon is in Utah as part of Intermountain Health’s “Let’s get to the bottom of colon cancer tour” and he only wants to help you.
The giant inflatable colon, whose name happens to be Collin, is 12 feet long and weighs 113 pounds. March is Colon Cancer Awareness Month, so Collin is traveling around Utah and Idaho to raise awareness about colon cancer and the various screening options. He is not going to change local weather patterns, eat small children, or take over local governments and raise your taxes.
Instead, Collin is planning to display “portions of a healthy colon, polyps or bumps on the colon, malignant polyps which look more vascular and have more redness, cancerous cells, advanced cancer cells, and Crohn’s disease,” KSL.com said.
Collin the colon is on loan to Intermountain Health from medical device manufacturer Boston Scientific and will be traveling to Spanish Fork, Provo, and Ogden, among other locations in Utah, as well as Burley and Meridian, Idaho, in the coming days.
Collin the colon’s participation in the tour has created some serious buzz in the Colin/Collin community:
- Colin Powell (four-star general and Secretary of State): “Back then, the second-most important topic among the Joint Chiefs of Staff was colon cancer screening. And the Navy guy – I can’t remember his name – was a huge fan of giant inflatable organs.”
- Colin Jost (comedian and Saturday Night Live “Weekend Update” cohost): “He’s funnier than Tucker Carlson and Pete Davidson combined.”
High caffeine levels may lower body fat, type 2 diabetes risks
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
the results of a new study suggest.
Explaining that caffeine has thermogenic effects, the researchers note that previous short-term studies have linked caffeine intake with reductions in weight and fat mass. And observational data have shown associations between coffee consumption and lower risks of type 2 diabetes and cardiovascular disease.
In an effort to isolate the effects of caffeine from those of other food and drink components, Susanna C. Larsson, PhD, of the Karolinska Institute, Stockholm, and colleagues used data from studies of mainly European populations to examine two specific genetic mutations that have been linked to a slower speed of caffeine metabolism.
The two gene variants resulted in “genetically predicted, lifelong, higher plasma caffeine concentrations,” the researchers note “and were associated with lower body mass index and fat mass, as well as a lower risk of type 2 diabetes.”
Approximately half of the effect of caffeine on type 2 diabetes was estimated to be mediated through body mass index (BMI) reduction.
The work was published online March 14 in BMJ Medicine.
“This publication supports existing studies suggesting a link between caffeine consumption and increased fat burn,” notes Stephen Lawrence, MBChB, Warwick (England) University. “The big leap of faith that the authors have made is to assume that the weight loss brought about by increased caffeine consumption is sufficient to reduce the risk of developing type 2 diabetes,” he told the UK Science Media Centre.
“It does not, however, prove cause and effect.”
The researchers agree, noting: “Further clinical study is warranted to investigate the translational potential of these findings towards reducing the burden of metabolic disease.”
Katarina Kos, MD, PhD, a senior lecturer in diabetes and obesity at the University of Exeter (England), emphasized that this genetic study “shows links and potential health benefits for people with certain genes attributed to a faster [caffeine] metabolism as a hereditary trait and potentially a better metabolism.”
“It does not study or recommend drinking more coffee, which was not the purpose of this research,” she told the UK Science Media Centre.
Using Mendelian randomization, Dr. Larsson and colleagues examined data that came from a genomewide association meta-analysis of 9,876 individuals of European ancestry from six population-based studies.
Genetically predicted higher plasma caffeine concentrations in those carrying the two gene variants were associated with a lower BMI, with one standard deviation increase in predicted plasma caffeine equaling about 4.8 kg/m2 in BMI (P < .001).
For whole-body fat mass, one standard deviation increase in plasma caffeine equaled a reduction of about 9.5 kg (P < .001). However, there was no significant association with fat-free body mass (P = .17).
Genetically predicted higher plasma caffeine concentrations were also associated with a lower risk for type 2 diabetes in the FinnGen study (odds ratio, 0.77 per standard deviation increase; P < .001) and the DIAMANTE consortia (0.84, P < .001).
Combined, the odds ratio of type 2 diabetes per standard deviation of plasma caffeine increase was 0.81 (P < .001).
Dr. Larsson and colleagues calculated that approximately 43% of the protective effect of plasma caffeine on type 2 diabetes was mediated through BMI.
They did not find any strong associations between genetically predicted plasma caffeine concentrations and risk of any of the studied cardiovascular disease outcomes (ischemic heart disease, atrial fibrillation, heart failure, and stroke).
The thermogenic response to caffeine has been previously quantified as an approximate 100 kcal increase in energy expenditure per 100 mg daily caffeine intake, an amount that could result in reduced obesity risk. Another possible mechanism is enhanced satiety and suppressed energy intake with higher caffeine levels, the researchers say.
“Long-term clinical studies investigating the effect of caffeine intake on fat mass and type 2 diabetes risk are warranted,” they note. “Randomized controlled trials are warranted to assess whether noncaloric caffeine-containing beverages might play a role in reducing the risk of obesity and type 2 diabetes.”
The study was supported by the Swedish Research Council for Health, Working Life and Welfare, Swedish Heart Lung Foundation, and Swedish Research Council. Dr. Larsson, Dr. Lawrence, and Dr. Kos have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM BMJ MEDICINE
What do I have? How to tell patients you’re not sure
Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.
Yet diagnostic uncertainty is an inevitable part of medicine.
“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.
By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.
“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.
To begin to answer these questions, The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.
For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.
Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.
- The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
- Next steps – lab tests, return visits, etc.
- Expected time frame for patient’s improvement and recovery.
- Full disclosure of the limitations of the physical examination or any lab tests.
- Ways to contact the physician going forward.
- Patient insights on their experience and reaction to what they just heard.
The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.
“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.
Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.
Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.
“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.
“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia.
Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty.
“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.
Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.
The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.
Yet diagnostic uncertainty is an inevitable part of medicine.
“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.
By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.
“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.
To begin to answer these questions, The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.
For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.
Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.
- The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
- Next steps – lab tests, return visits, etc.
- Expected time frame for patient’s improvement and recovery.
- Full disclosure of the limitations of the physical examination or any lab tests.
- Ways to contact the physician going forward.
- Patient insights on their experience and reaction to what they just heard.
The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.
“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.
Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.
Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.
“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.
“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia.
Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty.
“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.
Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.
The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Physicians often struggle with telling patients when they are unsure about a diagnosis. In the absence of clarity, doctors may fear losing a patient’s trust by appearing unsure.
Yet diagnostic uncertainty is an inevitable part of medicine.
“It’s often uncertain what is really going on. People have lots of unspecific symptoms,” said Gordon D. Schiff, MD, a patient safety researcher at Harvard Medical School and Brigham and Women’s Hospital in Boston.
By one estimate, more than one-third of patients are discharged from an emergency department without a clear diagnosis. Physicians may order more tests to try to resolve uncertainty, but this method is not foolproof and may lead to increased health care costs. Physicians can use an uncertain diagnosis as an opportunity to improve conversations with patients, Dr. Schiff said.
“How do you talk to patients about that? How do you convey that?” Dr. Schiff asked.
To begin to answer these questions, The scenarios included an enlarged lymph node in a patient in remission for lymphoma, which could suggest recurrence of the disease but not necessarily; a patient with a new-onset headache; and another patient with an unexplained fever and a respiratory tract infection.
For each vignette, the researchers also asked patient advocates – many of whom had experienced receiving an incorrect diagnosis – for their thoughts on how the conversation should go.
Almost 70 people were consulted (24 primary care physicians, 40 patients, and five experts in informatics and quality and safety). Dr. Schiff and his colleagues produced six standardized elements that should be part of a conversation whenever a diagnosis is unclear.
- The most likely diagnosis, along with any alternatives if this isn’t certain, with phrases such as, “Sometimes we don’t have the answers, but we will keep trying to figure out what is going on.”
- Next steps – lab tests, return visits, etc.
- Expected time frame for patient’s improvement and recovery.
- Full disclosure of the limitations of the physical examination or any lab tests.
- Ways to contact the physician going forward.
- Patient insights on their experience and reaction to what they just heard.
The researchers, who published their findings in JAMA Network Open, recommend that the conversation be transcribed in real time using voice recognition software and a microphone, and then printed for the patient to take home. The physician should make eye contact with the patient during the conversation, they suggested.
“Patients felt it was a conversation, that they actually understood what was said. Most patients felt like they were partners during the encounter,” said Maram Khazen, PhD, a coauthor of the paper, who studies communication dynamics. Dr. Khazen was a visiting postdoctoral fellow with Dr. Schiff during the study, and is now a lecturer at the Max Stern Yezreel Valley College in Israel.
Hardeep Singh, MD, MPH, a patient safety researcher at the Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine in Houston, called the new work “a great start,” but said that the complexity of the field warrants more research into the tool. Dr. Singh was not involved in the study.
Dr. Singh pointed out that many of the patient voices came from spokespeople for advocacy groups, and that these participants are not necessarily representative of actual people with unclear diagnoses.
“The choice of words really matters,” said Dr. Singh, who led a 2018 study that showed that people reacted more negatively when physicians bluntly acknowledged uncertainty than when they walked patients through different possible diagnoses. Dr. Schiff and Dr. Khazen’s framework offers good principles for discussing uncertainty, he added, but further research is needed on the optimal language to use during conversations.
“It’s really encouraging that we’re seeing high-quality research like this, that leverages patient engagement principles,” said Dimitrios Papanagnou, MD, MPH, an emergency medicine physician and vice dean of medicine at Thomas Jefferson University in Philadelphia.
Dr. Papanagnou, who was not part of the study, called for diverse patients to be part of conversations about diagnostic uncertainty.
“Are we having patients from diverse experiences, from underrepresented groups, participate in this kind of work?” Dr. Papanagnou asked. Dr. Schiff and Dr. Khazen said they agree that the tool needs to be tested in larger samples of diverse patients.
Some common themes about how to communicate diagnostic uncertainty are emerging in multiple areas of medicine. Dr. Papanagnou helped develop an uncertainty communication checklist for discharging patients from an emergency department to home, with principles similar to those that Dr. Schiff and Dr. Khazen recommend for primary care providers.
The study was funded by Harvard Hospitals’ malpractice insurer, the Controlled Risk Insurance Company. The authors disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Firing patients
One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.
While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.
What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.
In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.
If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.
If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.
The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.
You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.
When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.
Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.
Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.
While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.
What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.
In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.
If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.
If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.
The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.
You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.
When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.
Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.
Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
One might assume that, just as patients are free to accept or reject their doctors, physicians have an equal right to reject their patients; to a certain extent, that is true. There are no specific laws prohibiting a provider from terminating a patient relationship for any reason, other than a discriminatory one – race, nationality, religion, age, gender, sexual orientation, and so on. However, the evolution of ever-larger practice environments has raised new questions.
While verbal abuse, inappropriate treatment demands (particularly for controlled substances), refusal to adhere to mutually agreed treatment plans, and failure to keep appointments or pay bills remain the most common reasons for dismissal, evolving practice environments may require us to modify our responses.
What happens, for example, when a patient is banned from a large clinic that employs most of that community’s physicians, or is the only practice in town with the specialists required by that patient? The medical profession does have an obligation to not exclude such patients from care.
In a large cross-specialty system or consolidated specialist practice, firing a patient has a very different level of consequences than in a small office. There must be a balance between separating patients and doctors who don’t get along and seeing that the patient in question receives competent treatment. The physician, as the professional, has a higher standard to live up to with respect to handling this kind of situation.
If the problem is a personality conflict, the solution may be as simple as transferring the patient to another caregiver within the practice. While it does not make sense for a patient to continue seeing a doctor who does not want to see them, it also does not make sense to ban a patient from a large system where there could well be one or more other doctors who would be a good match. If a patient is unable to pay outstanding bills, a large clinic might prohibit them from making new appointments until they have worked out a payment plan rather than firing them outright.
If you are part of a large practice, take the time to research your group’s official policies for dealing with such situations. If there is no written policy, you might want to start that discussion with your colleagues.
The point is that in any practice, large or small, firing a patient should be a last resort. Try to make every effort to resolve the problem amicably. Communicate with the patient in question, explain your concerns, and discuss options for resolution. Take time to listen to the patient, as they may have an explanation (rational or not) for their objectionable behavior.
You can also send a letter, repeating your concerns and proposed solutions, as further documentation of your efforts to achieve an amicable resolution. All verbal and written warnings must, of course, be documented. If the patient has a managed care policy, we review the managed care contract, which sometimes includes specific requirements for dismissal of its patients.
When such efforts fail, we send the patient two letters – one certified with return receipt, the other by conventional first class, in case the patient refuses the certified copy – explaining the reason for dismissal, and that care will be discontinued in 30 days from the letter’s date. (Most attorneys and medical associations agree that 30 days is sufficient reasonable notice.) We offer to provide care during the interim period, include a list of names and contact information for potential alternate providers, and offer to transfer records after receiving written permission.
Following these precautions will usually protect you from charges of “patient abandonment,” which is generally defined as the unilateral severance by the physician of the physician-patient relationship without giving the patient sufficient advance notice to obtain the services of another practitioner, and at a time when the patient still requires medical attention.
Some states have their own unique definitions of patient abandonment. You should check with your state’s health department, and your attorney, for any unusual requirements in your state, because violating them could lead to intervention by your state licensing board. There is also the risk of civil litigation, which is typically not covered by malpractice policies, and may not be covered by your general liability policy either.
Dr. Eastern practices dermatology and dermatologic surgery in Belleville, N.J. He is the author of numerous articles and textbook chapters, and is a longtime monthly columnist for Dermatology News. Write to him at [email protected].
Adherence to DASH diet reduced risk of COPD
Greater adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a significantly reduced risk of chronic obstructive pulmonary disease (COPD) and improved lung function, based on data from more than 28,000 individuals in the United States.
but the effects of specific diet models such as the DASH diet and Mediterranean diet on COPD in particular has not been well studied, Jingli Wen, MD, of Nanjing Medical University, Jiangsu, China, and colleagues wrote.
In a study published in Frontiers in Nutrition, the researchers reviewed data from 28,605 adult participants in the National Health and Nutrition Examination Survey from 1999 to 2018.
The study population included 2,488 individuals with COPD participants and 25,607 individuals without COPD; the mean ages of the COPD and non-COPD groups were 60.2 years and 56.9 years, and the proportion of women was 63.7% and 51.4%, respectively. The primary outcome was the prevalence of COPD, defined as self-reports of a diagnosis of chronic bronchitis or emphysema. DASH diet scores were based on consumption of nine target nutrients: saturated fat, total fat, protein, cholesterol, fiber, magnesium, calcium, potassium, and sodium. Scores for compliance with the Mediterranean diet were based on intake of eight food categories: fruits, vegetables, legumes, fish, red meat, dairy products, alcohol, and olive oil.
Overall, a higher score for adherence to the DASH diet was significantly associated with a lower COPD risk (odds ratio, 0.83; P = .021). This association remained significant in subgroups of younger adults (OR, 0.74), men (OR, 0.73), and smokers (OR, 0.82).
By contrast, adherence to the Mediterranean diet was not significantly associated with COPD prevalence (OR, 1.03; P = .697).
The researchers also found a correlation between DASH diet adherence and improved lung function, especially among individuals without COPD. The risk of FEV1: forced vital capacity decrease, as well as dyspnea, cough, and expectoration, were negatively associated with greater adherence to the DASH diet, but greater adherence to the Mediterranean diet was only negatively associated with cough risk.
The relationship between the DASH diet and reduced COPD risk persisted after adjusting for occupational exposure and excluding participants with cardiovascular disease, cancer, or diabetes.
The current study is the first known to focus on the association between DASH diet and the risk of COPD among adults in the United States, the researchers wrote. The lack of effect of the Mediterranean diet on COPD, in contrast to some studies in other countries, “suggests that regional differences in diet may affect the role of diet in the development of COPD.”
The study findings were limited by several factors including the cross-sectional design that prevented conclusions of causality, the researchers noted. Other limitations included the lack of data of the impact of poor living habits, such as smoking, on food decisions, the use of short-term 24-hour dietary recall, and the reliance of self-reports for a diagnosis of COPD.
However, the results support the role of diet in COPD pathogenesis and expand the knowledge of relationships between the DASH diet and major chronic diseases, the researchers said. More prospective studies and clinical intervention studies are needed, but the findings should encourage clinicians to consider the potential role of a healthy diet in promoting lung health.
The study was supported by the Department of Health, Jiangsu Province, China. The researchers had no financial conflicts to disclose.
Greater adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a significantly reduced risk of chronic obstructive pulmonary disease (COPD) and improved lung function, based on data from more than 28,000 individuals in the United States.
but the effects of specific diet models such as the DASH diet and Mediterranean diet on COPD in particular has not been well studied, Jingli Wen, MD, of Nanjing Medical University, Jiangsu, China, and colleagues wrote.
In a study published in Frontiers in Nutrition, the researchers reviewed data from 28,605 adult participants in the National Health and Nutrition Examination Survey from 1999 to 2018.
The study population included 2,488 individuals with COPD participants and 25,607 individuals without COPD; the mean ages of the COPD and non-COPD groups were 60.2 years and 56.9 years, and the proportion of women was 63.7% and 51.4%, respectively. The primary outcome was the prevalence of COPD, defined as self-reports of a diagnosis of chronic bronchitis or emphysema. DASH diet scores were based on consumption of nine target nutrients: saturated fat, total fat, protein, cholesterol, fiber, magnesium, calcium, potassium, and sodium. Scores for compliance with the Mediterranean diet were based on intake of eight food categories: fruits, vegetables, legumes, fish, red meat, dairy products, alcohol, and olive oil.
Overall, a higher score for adherence to the DASH diet was significantly associated with a lower COPD risk (odds ratio, 0.83; P = .021). This association remained significant in subgroups of younger adults (OR, 0.74), men (OR, 0.73), and smokers (OR, 0.82).
By contrast, adherence to the Mediterranean diet was not significantly associated with COPD prevalence (OR, 1.03; P = .697).
The researchers also found a correlation between DASH diet adherence and improved lung function, especially among individuals without COPD. The risk of FEV1: forced vital capacity decrease, as well as dyspnea, cough, and expectoration, were negatively associated with greater adherence to the DASH diet, but greater adherence to the Mediterranean diet was only negatively associated with cough risk.
The relationship between the DASH diet and reduced COPD risk persisted after adjusting for occupational exposure and excluding participants with cardiovascular disease, cancer, or diabetes.
The current study is the first known to focus on the association between DASH diet and the risk of COPD among adults in the United States, the researchers wrote. The lack of effect of the Mediterranean diet on COPD, in contrast to some studies in other countries, “suggests that regional differences in diet may affect the role of diet in the development of COPD.”
The study findings were limited by several factors including the cross-sectional design that prevented conclusions of causality, the researchers noted. Other limitations included the lack of data of the impact of poor living habits, such as smoking, on food decisions, the use of short-term 24-hour dietary recall, and the reliance of self-reports for a diagnosis of COPD.
However, the results support the role of diet in COPD pathogenesis and expand the knowledge of relationships between the DASH diet and major chronic diseases, the researchers said. More prospective studies and clinical intervention studies are needed, but the findings should encourage clinicians to consider the potential role of a healthy diet in promoting lung health.
The study was supported by the Department of Health, Jiangsu Province, China. The researchers had no financial conflicts to disclose.
Greater adherence to the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a significantly reduced risk of chronic obstructive pulmonary disease (COPD) and improved lung function, based on data from more than 28,000 individuals in the United States.
but the effects of specific diet models such as the DASH diet and Mediterranean diet on COPD in particular has not been well studied, Jingli Wen, MD, of Nanjing Medical University, Jiangsu, China, and colleagues wrote.
In a study published in Frontiers in Nutrition, the researchers reviewed data from 28,605 adult participants in the National Health and Nutrition Examination Survey from 1999 to 2018.
The study population included 2,488 individuals with COPD participants and 25,607 individuals without COPD; the mean ages of the COPD and non-COPD groups were 60.2 years and 56.9 years, and the proportion of women was 63.7% and 51.4%, respectively. The primary outcome was the prevalence of COPD, defined as self-reports of a diagnosis of chronic bronchitis or emphysema. DASH diet scores were based on consumption of nine target nutrients: saturated fat, total fat, protein, cholesterol, fiber, magnesium, calcium, potassium, and sodium. Scores for compliance with the Mediterranean diet were based on intake of eight food categories: fruits, vegetables, legumes, fish, red meat, dairy products, alcohol, and olive oil.
Overall, a higher score for adherence to the DASH diet was significantly associated with a lower COPD risk (odds ratio, 0.83; P = .021). This association remained significant in subgroups of younger adults (OR, 0.74), men (OR, 0.73), and smokers (OR, 0.82).
By contrast, adherence to the Mediterranean diet was not significantly associated with COPD prevalence (OR, 1.03; P = .697).
The researchers also found a correlation between DASH diet adherence and improved lung function, especially among individuals without COPD. The risk of FEV1: forced vital capacity decrease, as well as dyspnea, cough, and expectoration, were negatively associated with greater adherence to the DASH diet, but greater adherence to the Mediterranean diet was only negatively associated with cough risk.
The relationship between the DASH diet and reduced COPD risk persisted after adjusting for occupational exposure and excluding participants with cardiovascular disease, cancer, or diabetes.
The current study is the first known to focus on the association between DASH diet and the risk of COPD among adults in the United States, the researchers wrote. The lack of effect of the Mediterranean diet on COPD, in contrast to some studies in other countries, “suggests that regional differences in diet may affect the role of diet in the development of COPD.”
The study findings were limited by several factors including the cross-sectional design that prevented conclusions of causality, the researchers noted. Other limitations included the lack of data of the impact of poor living habits, such as smoking, on food decisions, the use of short-term 24-hour dietary recall, and the reliance of self-reports for a diagnosis of COPD.
However, the results support the role of diet in COPD pathogenesis and expand the knowledge of relationships between the DASH diet and major chronic diseases, the researchers said. More prospective studies and clinical intervention studies are needed, but the findings should encourage clinicians to consider the potential role of a healthy diet in promoting lung health.
The study was supported by the Department of Health, Jiangsu Province, China. The researchers had no financial conflicts to disclose.
FROM FRONTIERS IN NUTRITION
Can particles in dairy and beef cause cancer and MS?
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?
However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.
In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.
Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
Acid radicals
However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.
According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
Viral progeny
In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.
The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
‘Breast milk is healthy’
Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.
The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
Colon cancer
To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.
The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
Institutional skepticism
When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?
The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.
BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.
Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
Association with MS?
Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”
However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.
Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.
This article was translated from the Medscape German Edition. A version appeared on Medscape.com.
Treat together: Tackle heart disease and obesity simultaneously
say the authors of a new state-of-the-art review.
“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.
The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.
And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.
Obesity can also alter drug pharmacokinetics and pharmacodynamics.
Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”
They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
Excess fat acts as filter and can skew diagnostic results
“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.
The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.
Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m2. In interventional radiology, there may be poor visualization of target areas.
“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
Therapeutic challenges: Drugs may work differently
A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.
Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.
Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.
Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
Cardiac rehabilitation is an intervention opportunity
Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.
But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.
“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.
The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”
Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.
A version of this article first appeared on Medscape.com.
say the authors of a new state-of-the-art review.
“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.
The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.
And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.
Obesity can also alter drug pharmacokinetics and pharmacodynamics.
Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”
They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
Excess fat acts as filter and can skew diagnostic results
“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.
The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.
Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m2. In interventional radiology, there may be poor visualization of target areas.
“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
Therapeutic challenges: Drugs may work differently
A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.
Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.
Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.
Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
Cardiac rehabilitation is an intervention opportunity
Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.
But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.
“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.
The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”
Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.
A version of this article first appeared on Medscape.com.
say the authors of a new state-of-the-art review.
“CVD and obesity are common conditions that frequently coexist. We cannot treat one of these conditions while ignoring the other,” Rosana G. Bianchettin, MD, of the division of cardiovascular diseases, Mayo Clinic, Rochester, Minn., and colleagues wrote in their review, recently published in the Journal of the American College of Cardiology.
The review outlines, for example, how obesity can impair common imaging tests used to diagnose heart disease, potentially reducing their accuracy.
And cardiac procedures such as percutaneous coronary intervention, open heart surgery, and revascularization all involve greater risk in the setting of obesity, while procedures such as valve replacement and heart transplantation carry a greater likelihood of failure.
Obesity can also alter drug pharmacokinetics and pharmacodynamics.
Weight reduction is an important part of the management of patients with cardiovascular disease and obesity, and “cardiac rehabilitation programs represent a potential opportunity for structured interventions,” the authors noted. However, “when other measures are insufficient, bariatric surgery can improve outcomes.”
They also advised against relying solely on body mass index (BMI) to assess adiposity: “It is prudent to investigate a range of complementary ... parameters alongside standard BMI calculations (accounting for age, race, and sex), including measures of central obesity, such as waist circumference, waist-to-hip ratio, and weight-to-height ratio.”
Excess fat acts as filter and can skew diagnostic results
“Obesity affects nearly all the diagnostic tests used in cardiology, such as ECG, CT scan, MRI, and echocardiogram,” senior author Francisco Lopez-Jimenez, MD, director of preventive cardiology at Mayo Clinic, explained in a statement.
The review includes a detailed table of these key obesity-related challenges. With electrocardiograms, for example, obesity can cause displacement of the heart, increased cardiac workload, and widening of the distance between the heart and the recording electrodes.
Obesity also lowers the sensitivity of exercise echocardiography, and use of CT coronary angiogram is completely precluded in people with a BMI above 40 kg/m2. In interventional radiology, there may be poor visualization of target areas.
“Excess fat acts as a kind of filter and can skew test readings to under- or overdiagnosis,” noted Dr. Lopez-Jimenez.
Therapeutic challenges: Drugs may work differently
A longer table in the review summarizes the therapeutic challenges involved in lifestyle modification, pharmacology, cardiac procedures, and other therapeutic measures for people with the two conditions.
Obesity can limit a person’s ability to exercise, for example, and smoking cessation may promote overeating and further weight gain.
Moreover, “tailoring pharmacotherapy is difficult because of unique pharmacokinetic and pharmacodynamic factors in people with obesity that alter distribution, metabolism, and elimination of drugs. Each drug also has special properties that must be considered when it is administrated,” the authors wrote.
Examples include the higher volume of distribution of lipophilic drugs in those with increased fat mass, alterations in liver metabolism, and difficulties with anticoagulant dosing.
Cardiac rehabilitation is an intervention opportunity
Although cardiac rehabilitation is “a cornerstone in secondary prevention” for people who have experienced a cardiac event, only 8% of such programs include formal in-house behavioral weight-loss programs.
But that could be remedied and expanded with the use of options such as home-based rehabilitation and telephone counseling, particularly in rural communities, Dr. Bianchettin and colleagues said.
“Motivated individuals will benefit from multicomponent approaches and should be encouraged to set specific, proximal, shared goals with their health care professional. A multitude of tools are available to support self-monitoring (e.g., smartphone applications, food diaries), and scheduled regular follow-up and feedback on progress can help to maintain motivation,” they wrote.
The bottom line, said Dr. Lopez-Jimenez: “Obesity is an important risk factor to address in patients with heart disease and it requires us to do something. ... The patient needs to know that their clinician can help them lose weight. Overall, weight-loss solutions come down to finding the right therapy for the patient.”
Dr. Bianchettin reported no relevant financial relationships. Dr. Lopez-Jimenez has reported conducting research related to 3D body assessment with Select Research, Mayo Clinic, and may benefit in the future if the technology is commercialized; he has not received any relevant monetary, financial, or other type of compensation to date, in relationship to this arrangement. He is a member of the scientific advisory board for Novo Nordisk.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
‘Unheard of’ PAH improvement with novel drug: STELLAR
NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.
Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,
“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm−5 reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.
“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.
Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
‘A new hope’ for patients with PAH
Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.
“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.
“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.
But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.
The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
Death or clinical worsening cut by 84%
STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.
In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.
The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.
The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.
The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.
“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.
Drug binds activin, a pathologic driver of PAH
Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.
“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”
Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.
Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.
STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.
NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.
Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,
“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm−5 reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.
“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.
Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
‘A new hope’ for patients with PAH
Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.
“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.
“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.
But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.
The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
Death or clinical worsening cut by 84%
STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.
In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.
The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.
The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.
The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.
“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.
Drug binds activin, a pathologic driver of PAH
Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.
“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”
Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.
Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.
STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.
NEW ORLEANS – An investigational, first-in class agent that delivers a completely new type of intervention to patients with pulmonary arterial hypertension (PAH) scored a clear win in the STELLAR trial, the first to complete among three phase 3 trials that are testing this agent.
Sotatercept, administered subcutaneously every 3 weeks for 24 weeks, improved from baseline average 6-minute walk distance (6MWD) by a significant and clinically meaningful 40.8 meters, compared with placebo, for the trial’s primary efficacy endpoint (P < .001). The treatment also “delivered broad clinical benefit across multiple domains including hemodynamics, World Health Organization functional class, disease biomarkers, risk scores and patient-reported outcomes,” Marius M. Hoeper, MD, said at the joint scientific sessions of the American College of Cardiology and the World Heart Federation.
“These results establish the clinical utility of sotatercept, administered in combination with approved PAH therapies, as a new treatment for PAH,” added Dr. Hoeper, professor and deputy director of the department of respiratory medicine at Hannover (Germany) Medical School,
“The most important aspect was the hemodynamic improvement,” with sotatercept treatment, which led to an average 235 dyn/sec per cm−5 reduction in pulmonary vascular resistance from baseline and an average cut in pulmonary artery pressure of 13.9 mm Hg from baseline, compared with placebo, a result that’s “unheard of,” Dr. Hoeper said in a press conference during the meeting.
“With other tested agents we usually see very little improvement in pulmonary artery pressure. This is a signal that we achieved some reversing of the pathological changes in the pulmonary vessels that lead to” PAH, he added.
Simultaneously with his report the findings also appeared online in the New England Journal of Medicine.
‘A new hope’ for patients with PAH
Based on the reported findings, sotatercept is a “very exciting boutique molecule” that will “offer patients with PAH a very exciting new treatment,” commented Rhonda Cooper-DeHoff, PharmD, a designated discussant and a researcher at the University of Florida, Gainesville.
“This study is a new hope for patients with PAH. Until now, they’ve had really bad outcomes, but [in this study] we see significant differences in 6MWD, hemodynamics, and risk factors. Overall, I think the benefit is greater than the risk” it may pose to patients through potential adverse effects, commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, and another discussant at the meeting.
“The results are impressive” and “encouraging,” and “suggest that sotatercept may represent a new and clinically consequential addition to current medications for PAH,” wrote three clinicians from Canyons Region Intermountain Medical Center in Murray, Utah, in an editorial that accompanied the published report.
But the authors of the editorial also raised several cautions and concerns. They questioned the generalizability of the findings, noting that the patients with PAH enrolled in the study were all adults who were clinically stable and an average of more than 8 years out from their initial PAH diagnosis, and more than 90% were on stable treatment for PAH with two or three agents specific for treating the disorder. The study cohort also had a disproportionately high enrollment of patients with idiopathic (59%) or heritable (18%) forms of PAH, and the 15% of patients in the trial with connective tissue disease represented a disproportionately low prevalence of this PAH subtype.
The editorialists also called for “ongoing vigilance” for adverse effects from sotatercept treatment, although they acknowledged that the adverse effects reported to date from sotatercept are “largely reassuring.”
Death or clinical worsening cut by 84%
STELLAR randomized 323 patients at 91 sites in 21 countries with WHO Group 1 PAH and with WHO functional class II or III disease to receive either sotatercept or placebo for 24 weeks, with an option for treatment to continue beyond that until the last patient in the study reached 24 weeks on treatment, resulting in an overall median treatment duration of nearly 33 weeks.
In addition to the significant result for the primary endpoint, the 163 patients who received sotatercept had significant improvements, compared with 160 placebo-treated patients, for eight of nine secondary endpoints. The only secondary endpoint with a neutral result was for a measure of cognitive and emotional wellbeing, a parameter that was already at a normal level at baseline in most enrolled patients, Dr. Hoeper explained.
The incidence of either death or an event indicative of clinical worsening during the overall median follow-up of almost 33 weeks was 26.3% among the control patients and 5.5% among those who received sotatercept. This translated into a significant reduction for this endpoint of 84% with sotatercept treatment, compared with placebo.
The rates of treatment-emergent adverse events leading to discontinuation were roughly the same in the control and sotatercept arms, and the incidence of severe or serious treatment-emergent adverse events was higher among the control patients.
The most common adverse event on sotatercept was bleeding events, which occurred in 32% of those on sotatercept and in 16% of the control patients, but the events in the sotatercept arm were “mostly mild,” said Dr. Hoeper. The next most frequent adverse event during sotatercept treatment was appearance of telangiectasias, which occurred in 14% of those on sotatercept and in 4% of control patients.
“It’s an uncommon adverse event profile, but not unexpected for a drug with its mechanism of action,” he said.
Drug binds activin, a pathologic driver of PAH
Sotatercept is an engineered molecule that combines a section of a human immunoglobulin G molecule with a portion of the receptor for activin. This structure allows sotatercept to bind free activin molecules in a patient’s blood, thereby removing a key driver of the pulmonary vascular wall remodeling that is at the pathologic root of PAH.
“Hyperproliferation of blood vessel–wall cells” caused by activin signaling “is perhaps the most important driver of PAH,” Dr. Hoeper said. “Sotatercept allows us for the first time to target the underlying mechanism behind PAH.”
Still ongoing are the HYPERION and ZENITH phase 3 trials of sotatercept. HYPERION is enrolling patients with newly diagnosed or high-risk PAH and is expected to complete in 2028. ZENITH is enrolling patients with more advanced PAH and a higher mortality risk, with results expected in 2026.
Sotatercept has received “Breakthrough Therapy” designation and “Orphan Drug” designation by the Food and Drug Administration, and “Priority Medicines” designation and “Orphan Drug” designation by the European Medicines Agency for the treatment of PAH. One recent review estimated a worldwide PAH prevalence of about 3-4 cases/100,000, which for the United States translates into a total prevalence of perhaps 10,000-15,000 affected people.
STELLAR was funded by Acceleron Pharma, a subsidiary of Merck. Dr. Hoeper is a consultant to Acceleron. Dr. Cooper-DeHoff, Dr. Grapsa, and the authors of the editorial on STELLAR have no relevant disclosures.
At ACC 2023