Mixed Topics

Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.

The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.

Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.

The study was published online March 23, 2022, in the BMJ.

“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.

One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.

Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.

“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.

In addition, he also emphasized that an observational study cannot establish causation.

For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.

The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”

Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
 

Study details

The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.

They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.

The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).

Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.

Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.

This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).

The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.

The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.

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

Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.

The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.

Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.

The study was published online March 23, 2022, in the BMJ.

“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.

One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.

Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.

“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.

In addition, he also emphasized that an observational study cannot establish causation.

For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.

The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”

Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
 

Study details

The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.

They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.

The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).

Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.

Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.

This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).

The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.

The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.

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

Antidopaminergic antiemetics (ADAs) that are widely used for nausea and vomiting, including that related to chemotherapy, have been associated with an increased risk of ischemic stroke in a new study from France.

The authors found that ADA users could be at a threefold increased risk of stroke shortly after the initiation of treatment.

Further analysis showed that all three ADAs studied (domperidone, metopimazine, and metoclopramide) were associated with an increased risk, especially in the first days of use, but the highest increase was found for metopimazine and metoclopramide.

The study was published online March 23, 2022, in the BMJ.

“Our results show that the risk of ischemic stroke appears to be associated with ADA use,” wrote the authors, led by Anne Bénard-Laribière, PharmD, MS, of the University of Bordeaux (France). They emphasized, however, that this is an observational study and cannot therefore establish causation.

One important note about this study is that patients with a history of cancer were specifically excluded. The authors did not elaborate on what the ADAs were being used for, other than to say that ADAs are used for nausea and vomiting of “variable origins,” and a press release noted that these drugs are often used by patients with migraine.

Hence it is not clear what relevance these findings have for patients with cancer, suggested an expert unrelated to the study, Ian Olver, MD, PhD, professorial research fellow, faculty of health and medical sciences, University of Adelaide.

“So the best that can be said, from my viewpoint, is that the ADAs studied have been associated with an increased risk of stroke in patients other than cancer patients,” he told this news organization.

In addition, he also emphasized that an observational study cannot establish causation.

For their study, the authors used data from the nationwide reimbursement database. Hence, they “needed to make the assumption that the date of reimbursement approximated to the date of administration, and that would not be the case for drugs used prophylactically prior to chemotherapy or radiotherapy,” Dr. Olver commented.

The authors were also unable to make any statement about dose and schedule. “Certainly chemotherapy-induced nausea and vomiting would require more intermittent dosing compared to noncancer uses,” Dr. Olver said. In addition, “metoclopramide in conventional doses is not very effective for this purpose and metopimazine is mainly used in Europe.”

Most patients with cancer would not be receiving these drugs, he suggested: “These days they would be receiving 5HT3 receptor antagonists and NK1 receptor antagonists and steroids.”
 

Study details

The French study investigated the risk of ischemic stroke associated with ADA use in a real-world setting. The authors conducted a case-time-control study using data from the nationwide French reimbursement health care system database Système National des Données de Santé.

They identified 2,612 patients from the database who had experienced a first ischemic stroke between 2012 and 2016 and had also received at least one reimbursement for domperidone, metopimazine, or metoclopramide during the 70-day period prior to their stroke.

The frequency of reimbursements for ADAs was compared with a risk period (1-14 days before a stroke) and three matched reference periods (57-70 days, 43-56 days, and 29-42 days before stroke).

Patients who had experienced a stroke were matched to a control group of 21,859 randomly selected healthy people who also received an ADA in the same time period.

Within the stroke cohort, 1,250 patients received an ADA at least once during the designated risk period and 1,060 in the reference periods. Among the controls, 5,128 and 13,165 received an ADA at least one time in the risk and reference periods, respectively.

This yielded a case-time-control ratio of adjusted odds ratios of 3.12, of a risk of stroke among new users. Stratification by age (<70 years and ≥70 years), sex, history of dementia, and gastroenteritis epidemic periods revealed similar results, although the highest case-time-control ratio observed in men(aOR, 3.59).

The risk of stroke appeared to increase for all ADAs, but the highest was for metopimazine (3.62-fold increase) and metoclopramide (a 3.53-fold increase), which are both drugs that have the ability to cross the blood-brain barrier.

The study was funded by Agence Nationale de Sécurité du Médicament et des Produits de Santé through a partnership with the Health Product Epidemiology Scientific Interest Group. All authors had financial support from ANSM for the submitted work; one coauthor disclosed relationships with Pfizer and Roche. Dr. Olver disclosed no relevant financial relationships.

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

Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.

Prevention of depression

Dr. Diener told the story of how he stumbled upon an interesting article in JAMA  in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.

As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.

This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
 

Beginning with the Inuit

It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.

Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
 

Disappointing study results

On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.

The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.

Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.

“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
 

Potential adverse effects

Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.

In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.

As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.

According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).

In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).

In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).

The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.

Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.

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

Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.

Prevention of depression

Dr. Diener told the story of how he stumbled upon an interesting article in JAMA  in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.

As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.

This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
 

Beginning with the Inuit

It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.

Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
 

Disappointing study results

On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.

The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.

Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.

“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
 

Potential adverse effects

Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.

In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.

As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.

According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).

In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).

In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).

The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.

Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.

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

Dietary supplements that contain omega-3 fatty acids have been widely consumed for years. Researchers have been investigating the benefits of such preparations for cardiovascular, neurologic, and psychological conditions. A recently published study on omega-3 fatty acids and depression inspired neurologist Hans-Christoph Diener, MD, PhD, of the Institute for Epidemiology at the University Duisburg-Essen (Germany), to examine scientific publications concerning omega-3 fatty acids or fish-oil capsules in more detail.

Prevention of depression

Dr. Diener told the story of how he stumbled upon an interesting article in JAMA  in December 2021. It was about a placebo-controlled study that investigated whether omega-3 fatty acids can prevent incident depression.

As the study authors reported, treatment with omega-3 preparations in adults aged 50 years or older without clinically relevant symptoms of depression at study initiation was associated with a small but statistically significant increase in the risk for depression or clinically relevant symptoms of depression. There was no difference in mood scale value, however, over a median follow-up of 5.3 years. According to the study authors, these results did not support the administration of omega-3 preparations for the prevention of depression.

This study was, as Dr. Diener said, somewhat negative, but it did arouse his interest in questions such as what biological effects omega-3 fatty acids have and what is known “about this topic with regard to neurology,” he said. When reviewing the literature, he noticed that there “were association studies, i.e., studies that describe that the intake of omega-3 fatty acids may possibly be associated with a lower risk of certain diseases.”
 

Beginning with the Inuit

It all started “with observations of the Inuit [population] in Greenland and Alaska after World War II, because it was remarked upon that these people ate a lot of fish and seal meat and had a very low incidence of cardiovascular diseases.” Over the years, a large number of association studies have been published, which may have encouraged the assumption that omega-3 fatty acids have positive health effects on various conditions, such as cardiovascular diseases, hyperlipidemia, type 2 diabetes, various malignancies, cognitive impairments, Alzheimer’s disease, depression and anxiety disorders, heart failure, slipped disks, ADHD, symptoms of menopause, rheumatoid arthritis, asthma, periodontitis, epilepsy, chemotherapy tolerance, premenstrual syndrome, and nonalcoholic fatty liver disease.

Dr. Diener believes that the problem is that these are association studies. But association does not mean that there is a causal relationship.
 

Disappointing study results

On the contrary, the results from the randomized placebo-controlled studies are truly frustrating, according to the neurologist. A meta-analysis of the use of omega-3 fatty acids in cardiovascular diseases included 86 studies with over 162,000 patients. According to Dr. Diener, it did not reveal any benefit for overall and cardiovascular mortality, nor any benefit for the reduction of myocardial infarction and stroke.

The results did indicate a trend, however, for reduced mortality in coronary heart disease. Even so, the number needed to treat for this was 334, which means that 334 people would have to take omega-3 fatty acids for years to prevent one fatal cardiac event.

Aside from this study, Dr. Diener found six studies on Alzheimer’s disease and three studies on dementia with patient populations between 600 and 800. In these studies, too, a positive effect of omega-3 fatty acids could not be identified. Then he discovered another 31 placebo-controlled studies of omega-3 fatty acids for the treatment or prevention of depression and anxiety disorder. Despite including 50,000 patients, these studies also did not show any positive effect.

“I see a significant discrepancy between the promotion of omega-3 fatty acids, whether it’s on television, in the ‘yellow’ [journalism] press, or in advertisements, and the actual scientific evidence,” said Dr. Diener. “At least from a neurological perspective, there is no evidence that omega-3 fatty acids have any benefit. This is true for strokes, dementia, Alzheimer’s disease, depression, and anxiety disorders.”
 

Potential adverse effects

Omega-3 fatty acids also have potentially adverse effects. The VITAL Rhythm study recently provided evidence that, depending on the dose, preparations with omega-3 fatty acids may increase the risk for atrial fibrillation. As the authors wrote, the results do not support taking omega-3 fatty acids to prevent atrial fibrillation.

In 2019, the global market for omega-3 fatty acids reached a value of $4.1 billion. This value is expected to double by 2025, according to a comment by Gregory Curfman, MD, deputy editor of JAMA and lecturer in health care policy at Harvard Medical School, Boston.

As Dr. Curfman wrote, this impressive amount of expenditure shows how beloved these products are and how strongly many people believe that omega-3 fatty acids are beneficial for their health. It is therefore important to know the potential risks of such preparations. One such example for this would be the risk for atrial fibrillation.

According to Dr. Curfman, in the last 2 years, four randomized clinical studies have provided data on the risk for atrial fibrillation associated with omega-3 fatty acids. In the STRENGTH study, 13,078 high-risk patients with cardiovascular diseases were randomly assigned to one of two groups. The subjects received either a high dose (4 g/day) of a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) or corn oil. After a median of 42 months, there was no significant difference between the two groups in the primary composite cardiovascular endpoint, but more frequent atrial fibrillation in the omega-3 fatty acid group, compared with the corn oil group (2.2% vs. 1.3%; hazard ratio, 1.69; 95% confidence interval, 1.29-2.21; P < .001).

In the REDUCE-IT study, 8179 subjects were randomly assigned to a high dose (4 g/day, as in STRENGTH) of an omega-3 fatty acid preparation consisting of a purified EPA (icosapent ethyl) or mineral oil. After a median observation period of 4.9 years, icosapent ethyl was associated with a relative reduction of the primary composite cardiovascular endpoint by 25%, compared with mineral oil. As in the STRENGTH study, this study found that the risk for atrial fibrillation associated with omega-3 fatty acids, compared with mineral oil, was significantly higher (5.3% vs. 3.9%; P = .003).

In a third study (OMEMI), as Dr. Curfman reported, 1027 elderly patients who had recently had a myocardial infarction were randomly assigned to receive either a median dose of 1.8 g/day of omega-3 fatty acids (a combination of EPA and DHA) or corn oil. After 2 years, there was no significant difference between the two groups in primary composite cardiovascular endpoints, but 7.2% of the patients taking omega-3 fatty acids developed atrial fibrillation. In the corn oil group, this proportion was 4% (HR, 1.84; 95% CI, 0.98-3.45; P = .06).

The data from the four studies together indicate a potential dose-dependent risk for atrial fibrillation associated with omega-3 fatty acids, according to Dr. Curfman. At a dose of 4.0 g/day, there is a highly significant risk increase (almost double). With a median dose of 1.8 g/day, the risk increase (HR, 1.84) did not reach statistical significance. At a daily standard dose of 840 mg/day, an increase in risk could not be determined.

Dr. Curfman’s recommendation is that patients who take, or want to take, preparations with omega-3 fatty acids be informed of the potential development of arrhythmia at higher dosages. These patients also should undergo cardiological monitoring.

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

As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.

If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.

It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.

I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?

Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.

I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.

Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.

I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.

Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.

We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.

Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.

As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.

If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.

It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.

I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?

Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.

I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.

Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.

I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.

Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.

We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.

Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.

As they rolled me down the hallway to the OR, ceiling lights rhythmically passing above, I zoned out into a 1,000-mile stare. How did I get here? I started humming “Swing Low, Sweet Chariot,” praying for a miracle to happen. I thought back to my birth plan, meticulously crafted, a one-pager so that the no-nonsense labor and delivery nurses wouldn›t think me completely off my rocker. No C-section unless medically necessary. Those words laughed back at me – cackling, even. I’d planned out the whole birthing process and here we were, my team almost jogging me to the OR. I lay still, utterly gobsmacked and partially anesthetized.

If I squint my eyes and hallucinate just a bit, that is sort of what motherhood has been like.

It’s about knowing all the things that could go wrong and meeting the unplanned head-on. Motherhood has indeed been a whirlwind – so many physical, psychological, and emotional transformations. And to top it off, the added effort of giving birth in a pandemic. As an over-40 physician, you’d think I would have been better prepared.

I was, but in a sense, I was not. The knowledge, the wisdom, the experience of my medical training surrounded me, but even I panicked at times in the beginning: Am I feeding her correctly? Am I making enough food for her? Am I doing the best that I can for her? What more could I be doing for her?

Over time, I’ve learned to lighten up. Some. In those teachable moments with my daughter Gia, I’ve learned to not sugarcoat reality but encourage the hopeful. If Gia falls on the ground? “You’re okay, sweetie. Now get back up.” If Gia has a tantrum and starts hitting herself? “Honey, our hands are for hugs, not hurting ourselves. Let’s go play.” Eighty percent of motherhood right now is redirection and the other 20% is patience.

I remember this one time I was rushing out the door for work. After getting in the car with my keys, I realized I forgot my coffee back in the house. I left the car, went back in the house to grab the blessed joe, went back to the car, and couldn’t get in because it was locked. I panicked at that moment, went back inside the house, and found Gia playing with my extra key fob. My own daughter locked me out of my car. Of course, it wasn’t her fault. Deep breath and I offered her another kiss while simultaneously taking the key fob from her.

Before Gia could walk, she could climb the stairs in our home. Her father and I sometimes refer to her as “Lil Bamm-Bamm” because she is so strong. One day, Daddy was supposed to be watching her while Mommy was folding laundry upstairs. She was not allowed on the stairs, but what should I hear? Literally, the pitter-patter of little feet, running down the upstairs hallway. Her father had drifted off watching yet another episode of something Star Wars–related. My strong little girl made it up the stairs all by herself and Dad received a strong word. The Force was with me that day.

I would say that I feel like having a child ages you, but what does that really mean when you’re already old? I’ve become acutely aware of my lack of endurance, stamina, and bodily strength. My knees will creak when taking her upstairs to bed, an osseous dirge of a lullaby. Date nights become unintentionally less and less frequent. Friday night dress-up becomes Friday night dress-down. I’ve replaced stiletto heels with comfy sweats.

Once we put Gia down for the night, we are usually exhausted from the day, and the couch and TV are welcome respites. We exhale. As over-40 parents, we knew that having children late in life would bring its challenges. But I’d like to think that we are meeting them the best way that we can. Often I encourage my body to meet Gia at her eye level, see what she sees, play with her on her own terms, and match her energy. She absolutely loves it when I do this. I’m out of breath and my knees are sore by the end of our play session, but I wouldn’t have it any other way.

We are learning from each other. She has a bright and assertive personality, and I am protective of that innocence. Her innocence is without fear. I often wonder what she is thinking when I see her facial expressions. A side-eye, a fleeting giggle. Is she secretly contemplating the chronicity of the cosmos, or is it just gas? I look at her in stolen moments and still can’t believe that I grew a human inside me, and said human was extracted from me and is now walking around my house commanding her bidding. So surreal. The unromanticized, scientific ingredients that are at play from conception to delivery are nothing short of miraculous. And the miracles of parenting over 40 are present every day.

Dr. Tolliver is a family medicine physician at The Ohio State University Wexner Medical Center in Columbus. A version of this article first appeared on Medscape.com.

Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”¹

Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”² that harms the public image of psychiatry.³ Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”⁴ occupying the most powerful position on earth.

Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.⁵ Few have yet to make a sober case for the outright abolition of Section 7.3.⁶

Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?

Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.⁷ Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.

Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.

When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.⁸

The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.⁹

Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.¹⁰ Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?

The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.

The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,¹¹ in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.

Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
 

Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.

2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.

3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.

4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.

5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).

6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.

7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.

8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.

9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.

10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.

11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.

Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”¹

Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”² that harms the public image of psychiatry.³ Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”⁴ occupying the most powerful position on earth.

Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.⁵ Few have yet to make a sober case for the outright abolition of Section 7.3.⁶

Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?

Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.⁷ Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.

Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.

When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.⁸

The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.⁹

Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.¹⁰ Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?

The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.

The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,¹¹ in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.

Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
 

Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.

2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.

3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.

4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.

5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).

6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.

7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.

8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.

9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.

10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.

11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.

Since it appeared in the first edition of the American Psychiatric Association’s Principles of Medical Ethics in 1973, the “Goldwater rule” – often referred to in terms of where in the APA’s guideline it can be found, Section 7.3 – has placed a stringent prohibition on psychiatrists offering professional opinions about public figures “unless he or she has conducted an examination and has been granted proper authorization for such a statement.”¹

Some psychiatrists experienced the restrictive nature of Section 7.3 more acutely perhaps than ever during the Trump presidency. This spurred numerous articles criticizing the guideline as an outdated “gag rule”² that harms the public image of psychiatry.³ Some psychiatrists violated the rule to warn the public of the dangers of a president with “incipient dementia”⁴ occupying the most powerful position on earth.

Following President Trump’s exit from the White House, the alarm bells surrounding his presidency have quieted. Criticisms of the Goldwater rule, on the other hand, have persisted. Many of these criticisms now call for the rule to be refined, allowing for psychiatrists to give their professional opinions about public figures, but with certain guidelines on how to do so.⁵ Few have yet to make a sober case for the outright abolition of Section 7.3.⁶

Self-regulating and internal policing are important factors in the continued independence of the medical profession, and we should continue to hold each other to high professional standards. That being said, do psychiatrists need training wheels to prevent us from devolving into unprofessional social commentators? Other medical specialties do not see the need to implement a rule preventing their colleagues from expressing expertise in fear of embarrassment. Do we not have faith in our ability to conduct ourselves professionally? Is the Goldwater rule an admission of a juvenile lack of self-control within our field?

Not only do other medical specialties not forcibly handhold their members in public settings, but other “providers” in the realm of mental health likewise do not implement such strict self-restraints. Psychiatry staying silent on the matter of public figures leaves a void filled by other, arguably less qualified, individuals. Subsequently, the public discord risks being flooded with pseudoscientific pontification and distorted views of psychiatric illness. The cycle of speculating on the mental fitness of the president has outlived President Trump, with concerns about Joe Biden’s incoherence and waning cognition.⁷ Therein is an important argument to be made for the public duty of psychiatrists, with their greater expertise and clinical acumen, to weigh in on matters of societal importance in an attempt to dispel dangerous misconceptions.

Practical limitations are often raised and serve as the cornerstone for the Goldwater rule. Specifically, the limitation being that a psychiatrist cannot provide a professional opinion about an individual without a proper in-person evaluation. The psychiatric interview could be considered the most in-depth and comprehensive evaluation in all of medicine. Even so, is a trained psychiatrist presented with grandiosity, flight-of-ideas, and pressured speech unable to comment on the possibility of mania without a lengthy and comprehensive evaluation? How much disorganization of behavior and dialogue does one need to observe to recognize psychosis? For the experienced psychiatrist, many of these behavioral hallmarks are akin to an ST elevation on an EKG representing a heart attack.

When considering less extreme examples of mental affliction, such as depression and anxiety, many signs – including demeanor, motor activity, manner of speaking, and other aspects of behavior – are apparent to the perceptive psychiatrist without needing an extensive interview that dives into the depths of a person’s social history and childhood. After all, our own criteria for depression and mania do not require the presence of social stressors or childhood trauma. Even personality disorders can be reasonably postulated when a person behaves in a particular fashion. The recognition of transitional objects, items used to provide psychological comfort, including the “teddy bear sign” are common and scientifically studied methods to recognize personality disorder.⁸

The necessity for an in-person evaluation has become less compelling over the years. In our modern age, important social moments are memorialized in countless videos that are arguably more relevant, more accurate, and less subjective than a psychiatric interview. Furthermore, forensic psychiatrists routinely comment on individuals they have not examined for a variety of reasons, from postmortem analysis to the refusal of the client to be interviewed. Moreover, and with significant contradiction, many leaders in the field of psychiatry view integrated care, the practice of psychiatrists advising primary care doctors, often without even seeing patients, to be the future of psychiatry.⁹

Some reading this may scoff at the above examples. Perhaps Section 7.3 speaks to an underlying insecurity in our field regarding our ability to accurately diagnose. That insecurity is not unfounded. In terms of the DSM-5, the bar for reliability has been lowered to a kappa of 0.2-0.4, from a previous standard of 0.6, in an attempt to avoid critiques of unreliability.¹⁰ Yet herein lies a powerful recognition of the necessity of the Goldwater rule. If psychiatrists cannot reliably agree on the presence of diagnoses in the controlled setting of scientific study, how can we expect to speak with coherence and consistency on highly mediatized and provoking topics?

The defense – that the difficulty psychiatrists have at providing an accurate diagnosis stems from the immense complexity of the system being evaluated, the human mind – is a valid one. Attempts to force such complex pathology, with all its many variables, into the check-box approach implemented in the DSM inevitably leads to problems with diagnostic reliability. Still, as psychiatrists we retain a level of expertise in assessing and treating complex disorders of the mind that no other field can claim.

The duty physicians have not only to work toward the health of their individual patients, but also to act in service of the public health and well-being of communities in which our patients live, is well established. How ethical is it then for psychiatry to absolve itself from duty when it comes to public figures at the center of shaping public opinion? There are numerous recent, high-profile instances where our expertise may have helped shine light in an otherwise murky public discussion filled with disinformation. The death of George Floyd and the year of turmoil that followed is a salient example. The conservatorship of Britney Spears and the resulting societal outcry is another. Even setting the matter of diagnosis aside, we can help illuminate the societal implications of conservatorship laws,¹¹ in addition to providing input on how to safely and responsibly approach an individual who is in crisis, under the influence of multiple illicit substances, and possibly suffering from excited delirium.

Whether psychiatry has progressed enough as a medical specialty to trust ourselves with the option of providing professional opinions on public figures is an ongoing debate. The persistence of the Goldwater rule is a strong testament to the internal lack of confidence among psychiatrists regarding our ability to provide accurate diagnoses, act with integrity in the public space, and foster a positive public image. That lack of confidence may be well deserved. However, it is possible that our field will never go through the necessary pains of maturing as long as Section 7.3 remains in place.
 

Dr. Compton is a psychiatry resident at University of California, San Diego. His background includes medical education, mental health advocacy, work with underserved populations, and brain cancer research. Dr. Compton has no conflicts of interest. Dr. Badre is a clinical and forensic psychiatrist in San Diego. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Badre can be reached at his website, BadreMD.com. He has no conflicts of interest.

References

1. American Psychiatric Association. The principles of medical ethics with annotations especially applicable to psychiatry. Section 7. American Psychiatric Association; 2013 edition.

2. Glass LL. The Goldwater rule is broken. Here’s how to fix it. STAT News. 2018 June 18.

3. Plymyer D. The Goldwater rule paradox. 2020 Aug 7.

4. Lieberman JA. Trump’s brain and the 25th Amendment. Vice. 2017 Sep 8.

5. Blotcky AD et al. The Goldwater rule is fine, if refined. Here’s how to do it. Psychiatric Times. 2022 Jan 6;39(1).

6. Blotcky AD and Norrholm SD. After Trump, end the Goldwater rule once and for all. New York Daily News. 2020 Dec 22.

7. Stephens B. Biden should not run again – And he should say he won’t. New York Times. 2021 Dec 14.

8. Schmaling KB et al. The positive teddy bear sign: Transitional objects in the medical setting. J Nerv Ment Dis. 1994 Dec;182(12):725.

9. Badre N et al. Psychopharmacologic management in integrated care: Challenges for residency education. Acad Psychiatry. 2015; 39(4):466-9.

10. Kraemer HC et al. DSM-5: How reliable is reliable enough? Am J Psychiatry. 2012 Jan;169(1):13-5.

11. Badre N and Compton C. Britney Spears – Reflections on conservatorship. Clinical Psychiatry News. 2021 Nov 16.

BOSTON – Patients with recessive X-linked and autosomal recessive lamellar congenital ichthyosis (CI) achieved treatment success with a novel topical isotretinoin ointment known as TMB-001, results from a phase 2b study demonstrated.

“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”

In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.

ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.

TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.

For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.

Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.

Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).

“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”

Phase 3 trials of the agent are scheduled to begin in June of 2022.

Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”

Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.

*A change correcting the age range of the patients in the study was made on 3/29/22. 

BOSTON – Patients with recessive X-linked and autosomal recessive lamellar congenital ichthyosis (CI) achieved treatment success with a novel topical isotretinoin ointment known as TMB-001, results from a phase 2b study demonstrated.

“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”

In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.

ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.

TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.

For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.

Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.

Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).

“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”

Phase 3 trials of the agent are scheduled to begin in June of 2022.

Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”

Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.

*A change correcting the age range of the patients in the study was made on 3/29/22. 

BOSTON – Patients with recessive X-linked and autosomal recessive lamellar congenital ichthyosis (CI) achieved treatment success with a novel topical isotretinoin ointment known as TMB-001, results from a phase 2b study demonstrated.

“Patients with these deficiencies have generally had very limited treatment options, including lifelong use of emollients and keratolytics, and in severe cases, systemic retinoids,” Christopher G. Bunick, MD, PhD, associate professor of dermatology at Yale University, New Haven, Conn., said at a late-breaking abstract session at the annual meeting of the American Academy of Dermatology. “There is currently no [Food and Drug Administration]-approved drug for CI. So, imagine your patients and their parents, and the frustration they must feel.”

In a study known as CONTROL, he and his colleagues evaluated the effect of TMB-001 on two subtypes of congenital ichthyosis: X-linked recessive ichthyosis (XLRI) and autosomal recessive congenital ichthyosis–lamellar ichthyosis (ARCI-LI). Of the two, the most common is XLRI, which has an estimated incidence of 1:3,000 and is caused by a deficiency of steroid sulfatase, resulting in cholesterol sulfate accumulation in the stratum corneum, retained corneodesmosomes, and reduced corneocyte desquamation, Dr. Bunick said.

ARCI-LI is rarer, with a prevalence of 1:100,000, and has been linked to mutations in six genes, most commonly TGM1, resulting in enzyme inactivation and deficient cross-linking of cornified cell envelope proteins.

TMB-001 is a proprietary, novel, topical isotretinoin formulation to treat CI that is being developed by Timber Pharmaceuticals. It uses a patented “IPEG” technology isotretinoin delivery system designed specifically for patients with CI. In a prior phase 2a study, TMB-001 0.1% and 0.2% ointment twice a day demonstrated greater improvement in ≥ 1 and ≥ 2 Investigator Global Assessment (IGA) scores compared with vehicle. Scaling in all patients treated with TMB-001 was considered clear, almost clear, or mild at 8 weeks, and no concerning safety signals were observed.

For the current trial, 33 patients with genetically confirmed XLRI/ARCI-LI and ≥ 2 (out of 4) Visual Index for Ichthyosis Severity (VIIS) assessment areas with a ≥ 3 scaling score were randomized 1:1:1 to TMB-001 0.05%, TMB-001 0.1%, or vehicle twice daily for 12 weeks. Primary and secondary efficacy endpoints were reduction of ≥ 50% compared with baseline in VIIS-scaling (VIIS-50) and a ≥ 2-grade reduction in the Investigator Global Assessment (IGA)–scaling score compared with baseline. The patients ranged in age from 9 to 80 years, the majority were White, and their baseline body surface area (BSA) affected ranged from 28% to 38%.

Of the 33 patients, 11 patients received TMB-001 0.05%, 10 received TMB-001 0.1%, and 12 received the vehicle.

Among all patients, 55% had ARCI-LI and 45% had XLRI subtypes, and those with ARCI-LI had greater prior use of corticosteroid, emollient, and oral/topical retinoids. Overall, 100%, 50%, and 75% of patients with XLRI and 100%, 33%, and 17% of patients with ARCI-LI achieved VIIS-50 after receiving TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

An improvement of a ≥ 2-grade IGA score was observed in 100%, 50%, and 25% of patients with XLRI and 100%, 67%, and none of patients with ARCI-LI who received TMB-001 0.05%, TMB-001 0.1%, and vehicle, respectively.

Dr. Bunick reported that there were no serious adverse events, no hospitalizations, and no patient deaths. Six patients discontinued treatment, five because of participant withdrawal and one because of physician withdrawal. The four most common treatment-emergent adverse events were erythema (21%), pruritus (21%), pain (15%) and dermatitis (12%).

“These results support ongoing investigation of TMB-001 as a promising alternative to systemic retinoids for participants with CI,” Dr. Bunick concluded. He noted that while he is not privy to details of TMB-001’s IPEG delivery system, “the way they have used polyethylene glycol to encapsulate the isotretinoin allows for greater barrier penetration and reduces a lot of the tolerability issues that are seen with other topical retinoids.” In his view, “that is providing this retinoid a greater chance of success. The patented delivery system is not only designed to help the isotretinoin do its job, but also to provide that stability and the ability to compound it, which have been barriers to success in the past.”

Phase 3 trials of the agent are scheduled to begin in June of 2022.

Amy S. Paller, MD, professor and chair of the department of dermatology at Northwestern University, Chicago, who was asked to comment on the study, said that she was impressed that no significant changes from baseline laboratory clinical assessments were observed. “If that’s true, then we don’t have to be monitoring these patients in the same way as with systemic agents,” said Dr. Paller, who was involved in the phase 2a proof-of-concept trial of TMB-001. “I think that deserves more investigation. Hopefully that will be looked at in the phase 3 trial.”

Dr. Bunick reported having no disclosures related to his presentation. Dr. Paller disclosed that she is consultant to and/or an investigator for numerous pharmaceutical companies.

*A change correcting the age range of the patients in the study was made on 3/29/22. 

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

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

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

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

The Heartland virus is circulating in lone star ticks in Georgia, according to a new study published in Emerging Infectious Diseases.

People can get the virus after being bitten by an infected tick, which can lead to hospitalization and death. The virus has also been found among deer and other wild mammals.

“Heartland is an emerging infectious disease that is not well understood,” Gonzalo Vazquez-Prokopec, PhD, the senior study author and an expert in vector-borne diseases at Emory University, Atlanta, said in a statement.

“We’re trying to get ahead of this virus by learning everything that we can about it before it potentially becomes a bigger problem,” he said.

Researchers at Emory and the University of Georgia analyzed virus samples from nearly 10,000 ticks collected in central Georgia. They found that about 1 out of every 2,000 specimens had the Heartland virus, including the adult and nymph stages.

The virus, which was first identified in Missouri in 2009, has been documented in several states across the Southeast and Midwest. There have been more than 50 cases in people from 11 states, according to the Centers for Disease Control and Prevention, with most cases requiring hospitalization. Most people diagnosed with the disease became sick from May to September, the CDC reported. Symptoms can be a high fever, fatigue, diarrhea, muscle pain, and low counts of white blood cells and platelets. It can take up to 2 weeks for symptoms to appear after a bite from an infected tick.

There are no vaccines or medications to prevent or treat the Heartland virus, according to the CDC. Doctors may be able to provide medications to improve symptoms. Overall, though, experts recommend that people avoid tick bites as much as possible, particularly during “high tick season” between April and September.

“You should be thinking about them almost any time of the year. It’s something that should be on everybody’s mind,” Jonathan Larson, PhD, an extension entomologist at the University of Kentucky, Lexington, told USA Today.

The CDC recognizes 18 tick-borne diseases in the United States, including Lyme disease, which has become the most common vector-borne disease in the country. The black-legged tick, also known as the deer tick, typically transmits the bacteria that causes Lyme disease.

But researchers are still studying how the Heartland virus spreads. In the latest study, they found the virus in the lone star tick, which is named for a distinctive white spot on its back and is the most common tick in Georgia. The tick is also widely distributed in wooded areas across the Southeast, Midwest, and Eastern United States.

The research team will now collect ticks across Georgia for testing to better understand what could raise the risk of getting the Heartland virus.

“We want to start filling in the huge gaps of knowledge of the transmission cycle for Heartland virus,” Dr. Vazquez-Prokopec said. “We need to better understand the key actors that transmit the virus and any environmental factors that may help it to persist within different habitats.”

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

People with higher (above the median) consumption of artificial sweeteners – especially aspartame and acesulfame-potassium (acesulfame-K) – had a 13% higher risk of overall cancer over 8 years than those who did not consume these sweeteners.

Higher consumption of aspartame was associated with a 22% increased risk of breast cancer and a 15% increased risk of obesity-related cancer, compared with not consuming any of these sweeteners.*

BigRedCurlyGuy/Thinkstock

These findings from the Nutri-Santé population-based observational study in France were published online March 24, 2022, in PLoS Medicine.

“Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effect,” Charlotte Debras, of the French National Institute for Health and Medical Research (Inserm) and Sorbonne Paris Nord University, and colleagues wrote.

“Results from the NutriNet-Santé cohort (n = 102,865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo/in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies,” they wrote.

Commenting to the U.K. Science Media Center, Duane Mellor, PhD, registered dietitian and senior teaching fellow, Aston (England) University, said: “This study does not prove or even suggest that we should go back to sugar and turn our backs on artificial sweeteners or diet drinks.  

“It does, however, suggest that artificial sweeteners are not a perfect replacement for sugar, they come with their own potential risks, as does sugar. The ideal answer is probably to move away from both, however, that may be unappealing to many who like a little sweetness in their life, so ditching the regular or diet soft drink (soda) for water may not be a well-received health message.”
 

Important analysis, interpret with caution

“I think that this is an important analysis, but the results need to be interpreted with caution,” another expert, John L. Sievenpiper, MD, PhD, associate professor, departments of nutritional sciences and medicine, University of Toronto, said in an interview.

“Large observational studies like this one that assess the exposure to low and no calorie sweeteners with obesity-related chronic diseases are at risk of reverse causality,” he explained. This is “a caveat that is well recognized by investigators in this field ... and guideline and policy makers.”

Reverse causality is a possibility because “it is likely that many high consumers of low- and no-calorie sweeteners (of which aspartame and acesulfame-K are the most common) will be consuming these sweeteners as a weight-loss strategy,” he added, “as opposed to these sweeteners causing obesity and its complications (including cancers).”

His team recently published a Diabetes and Nutrition Study Group–commissioned systematic review and meta-analysis of 17 randomized controlled trials (JAMA Netw Open. 2022;5[3]:e222092). Their findings “suggest that over the moderate term [low- and no-calorie sweetened beverages] are a viable alternative to water as a replacement strategy in adults with overweight or obesity who are at risk for or have diabetes,” states one of two syntheses (the other is in press in Diabetes Care) for the update of the European Association for the Study of Diabetes guidelines coming in the fall of 2022. 

“The bottom line” for the current study, according to Dr. Sievenpiper, “is that it is difficult to disentangle the signals for low- and no-calorie sweeteners from obesity itself and the signals for the sugars and calories that they are replacing/displacing in this analysis. Substitution analyses would be useful to address some of these concerns.”
 

Conflicting results

Recent epidemiologic and animal studies about a possible link between artificial sweeteners and risk of cancer have had conflicting results, and information about specific types of sweeteners and consumption of artificially sweetened foods as well as beverages is lacking, Ms. Debras and colleagues wrote.

They aimed to investigate the associations between intakes of artificial sweeteners (total and the most common ones – aspartame, acesulfame-K, and sucralose) and cancer risk (overall risk and most frequent types – breast, prostate, and obesity-related cancers) in the ongoing NutriNet-Santé study.

“Obesity-related cancers are cancers for which obesity is involved in their etiology as one of the risk (or protective) factors, as recognized by the World Cancer Research Fund (independently of participant BMI [body mass index] status): colorectal, stomach, liver, mouth, pharynx, larynx, esophageal, breast (with opposite associations pre- and post menopause), ovarian, endometrial, and prostate cancers,” the researchers explained.

According to a recent study , “obesity increases the risk of breast cancer in postmenopausal women but, conversely, it appears to be protective in premenopausal women,” Dr. Sievenpiper noted.

The ongoing NutriNet-Santé study was initiated in 2009 to investigate associations between nutrition and health in the French population. Participants aged 18 and older with Internet access enroll voluntarily and self-report medical history and sociodemographic, diet, lifestyle, and health data.

The current cohort included 102,865 adults who enrolled in 2009-2021.

Consumption of artificial sweeteners was determined from repeated 24-hour dietary records that included brand names of processed foods.

At enrollment, participants were an average age of 42 years and 79% were women. They had a mean BMI of 24 kg/m2. On average, they had 5.6 dietary records.

Most participants did not consume artificial sweeteners (63%); those who did were classified as lower consumers (18.5%) or higher consumers (18.5%).

Aspartame was the most common artificial sweetener (58% of intake), followed by acesulfame-K (29%) and sucralose (10%), and these were mostly in soft drinks (53%), table-top sweeteners (29%), and yogurt/cottage cheese (8%). 

During a median 7.7-year follow-up, 3,358 incident cancers – 982 breast, 403 prostate, and 2023 obesity-related cancers – were diagnosed in participants who were a mean age of 60.

Compared with nonconsumers, higher consumers of artificial sweeteners had a higher risk of overall cancer (hazard ratio, 1.13; 95% confidence interval, 1.03-1.25; P-trend = .002), after adjusting for age, sex, education, physical activity, smoking, BMI, height, weight gain during follow-up, diabetes, family history of cancer, number of 24-hour dietary records, baseline caloric intake, and consumption of alcohol, sodium, saturated fatty acids, fiber, sugar, fruit and vegetables, whole-grain foods, and dairy products.

Participants who were higher consumers of aspartame had an increased risk of overall cancer (HR, 1.15; 95% CI, 1.03-1.28; P = .002), as did higher consumers of acesulfame-K (HR, 1.13; 95% CI, 1.01-1.26; P = .007), compared with nonconsumers, after adjusting for the multiple variables. 

Higher consumers of aspartame had a higher risk of breast cancer (HR, 1.22; 95% CI, 1.01-1.48; P = .036) and obesity-related cancers (HR, 1.15; 95% CI, 1.01-1.32; P = .026) than nonconsumers.

Higher consumers of total artificial sweeteners had a higher risk of obesity-related cancers than nonconsumers (HR, 1.13; 95% CI, 1.00-1.28; P = .036).

The researchers acknowledged that study limitations include potential selection bias, residual confounding, and reverse causality, though sensitivity analyses were performed to address these concerns.

The NutriNet-Santé study was supported by several French public institutions. Ms. Debras was supported by a grant from the French National Cancer Institute. This project has received funding from the European Research Council, the French National Cancer Institute, the French Ministry of Health, and the IdEx Université de Paris. Dr. Sievenpiper has reported receiving funding from the Tate and Lyle Nutritional Research Fund at the University of Toronto, the Nutrition Trialists Fund at the University of Toronto, and the International Sweeteners Association.

Correction, 3/31: An earlier version of this article erroneously stated that there was a 22% increased risk of overall cancer, rather than breast cancer. 

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

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

What are the principal microorganisms that cause puerperal mastitis?

Continue to the answer...

Staphylococci and Streptococcus viridans are the 2 dominant microorganisms that cause puerperal mastitis. For the initial treatment of mastitis, the drug of choice is dicloxacillin sodium (500 mg orally every 6 to 8 hours for 7 to 10 days). If the patient has a mild allergy to penicillin, cephalexin (500 mg orally every 6 to 8 hours for 7 to 10 days) is an appropriate alternative. If the allergy to penicillin is severe or if methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected, either clindamycin (300 mg orally twice daily for 7 to 10 days) or trimethoprim-sulfamethoxazole double strength orally twice daily for 7 to 10 days should be used.

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Only about 1 in 7 new cancer drugs approved in the U.S. displace existing standards of care, a new analysis shows.

Of more than 200 agents evaluated, most (42%) received approval as second-, third-, or later-line therapies.

“While there is justified enthusiasm for the high volume of new cancer drug approvals in oncology and malignant hematology, these approvals must be evaluated in the context of their use,” the authors note in a report published online March 15 in JAMA Network Open. Later-line drugs may, for instance, “benefit patients with few alternatives but also add to cost of care and further delay palliative and comfort services” compared to first-line therapies, which may alter “the treatment paradigm for a certain indication.”

The U.S. Food and Drug Administration approves several new cancer drugs each month, but it’s not clear how many transform the treatment landscape.

To investigate, David Benjamin, MD, with the Division of Hematology and Oncology, University of California, Irvine, and colleagues evaluated all 207 cancer drugs approved in the U.S. between May 1, 2016 and May 31, 2021.

The researchers found that only 28 drugs (14%) displaced the prior first-line standard of care for an indication.

Examples of these cancer drugs include alectinib for anaplastic lymphoma kinase rearrangement–positive metastatic non–small cell lung cancer (NSCLC), osimertinib for epidermal growth factor receptor exon 19 deletion or exon 21 L858R substitution NSCLC, atezolizumab plus bevacizumab for unresectable or metastatic hepatocellular carcinoma, and cabozantinib for advanced kidney cancer.

A total of 32 drugs (15%) were approved as first-line alternatives or new drugs. These drugs were approved for use in the first-line setting but did not necessarily replace the standard of care at the time of approval or were first-of-their-class therapies.

Examples of these drug approvals include apalutamide for nonmetastatic castrate-resistant prostate cancer, tepotinib for metastatic MET exon 14-skipping NSCLC, and avapritinib for unresectable or metastatic gastrointestinal stromal tumor with platelet-derived growth factor receptor alpha exon 18 variant, including D842V variant.

A total of 61 drugs (29%) were approved as add-on therapies for use in combination with a previously approved therapy or in the adjuvant or maintenance settings. These drugs “can only increase the cost of care,” the study team says.

Most new approvals (n = 86) were for use in second-, third- or later-line settings, often for patients for whom other treatment options had been exhausted.

The authors highlight disparities among approvals based on tumor type. Lung-related tumors received the most approvals (n = 37), followed by genitourinary tumors (n = 28), leukemia (n = 25), lymphoma (n = 22), breast cancer (n = 19), and gastrointestinal cancers (n = 14).

The authors note that cancer drugs considered new standards of care or approved as first-line setting alternatives could “provide market competition and work to lower cancer drug prices.”

The study was funded by a grant from Arnold Ventures.

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

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.

Can you keep it down? I’m trying to be boring

He chides his friends for not looking both ways before crossing the road. He is never questioned by the police because they fall asleep listening to him talk. He has won the office’s coveted perfect attendance award 10 years running. Look out, Dos Equis guy, you’ve got some new competition. That’s right, it’s the most boring man in the world.

For this boring study (sorry, study on boredom) conducted by English researchers and published in Personality and Social Psychology Bulletin, people were surveyed on various jobs and hobbies, ranking them by how exciting or boring they are, as well as how competent someone with those jobs/hobbies would be, their willingness to avoid someone with those jobs/hobbies, and how much they’d need to be paid to spend time with someone who had an undesirable job/hobby.

Courtesy Mohamed Hassan/pxhere

According to the British public, the most boring person in the world is a religious data analyst who likes to sleep and lives in a small town. In fact, spending time with this person is almost a full-time job on its own: To make it worth their while, survey subjects wanted 35 pounds a day. The boring person also was viewed as less competent, as is anyone with a boring job.

Now, there probably aren’t a lot of religious data analysts out there, but don’t worry, there are plenty of other boring jobs – accounting, tax/insurance, cleaning, and banking rounded out the top five (apparently people don’t like finances) – and hobbies – watching TV, observing animals, and mathematics filled out the top five. In case you’re curious, performing artists, scientists, journalists, health professionals, and teachers were viewed as having exciting jobs; exciting hobbies included gaming, reading, domestic tasks (really?), gardening, and writing.

Lead researcher Wijnand Van Tilburg, PhD, made an excellent point about people with boring jobs: They “have power in society – perhaps we should try not to upset them and stereotype them as boring!”

We think they should lean into it and make The Most Boring Man in the World ads: “When I drive a car off the lot, its value increases because I used the correct lending association. Batman trusts me with his Batmobile insurance. I can make those Cuban cigars tax exempt. Stay financially solvent, my friends.”
 

Fungi, but make it fashion

Fashion is an expensive and costly industry to sustain. Cotton production takes a toll on the environment, leather production comes with environmental and ethical/moral conundrums, and thanks to fast fashion, about 85% of textiles are being thrown away in the United States.

Courtesy Akram Zamani

Researchers at the University of Borås in Sweden, however, have found a newish solution to create leather, cotton, and other textiles. And as with so many of the finer things, it starts with unsold bread from the grocery store.

Akram Zamani, PhD, and her team take that bread and turn it into breadcrumbs, then combine it with water and Rhizopus delemar, a fungus typically found in decaying food. After a couple of days of feasting on the bread, the fungus produces natural fibers made of chitin and chitosan that accumulate in the cell walls. After proteins, lipids, and other byproducts are removed, the team is left with a jelly-like substance made of those fibrous cell walls that can be spun into a fabric.

The researchers started small with very thin nonpliable sheets, but with a little layering by using tree tannins for softness and alkali for strength, their fungal leather is more like real leather than competing fungal leathers. Not to mention its being able to be produced in a fraction of the time.

This new fungal leather is fast to produce, it’s biodegradable, and it uses only natural ingredients to treat the materials. It’s the ultimate environmental fashion statement.
 

Who’s afraid of cancer? Not C. elegans

And now, we bring you part 2 of our ongoing series: Creatures that can diagnose cancer. Last week, we discovered that ants are well on their way to replacing dogs in our medical labs and in our hearts. This week, we present the even-more-lovable nematode.

Courtesy Nari Jang

The soil-dwelling nematode Caenorhabditis elegans, which is less than 1 mm long, is known to be “attracted or repelled by certain odors, so we came up with an idea that the roundworm could be used to detect lung cancer,” Shin Sik Choi, PhD, of Myongji University in South Korea, who is the project’s principal investigator, said in a statement on Eurekalert.

Dr. Choi’s team created a “worm-on-a-chip” that allowed the nematodes to choose between a drop of culture media from lung cancer cells and media from normal lung fibroblasts. An hour after being placed in the chip’s central chamber, more nematodes had crawled toward the lung cancer media than the normal-cell sample.

The investigators estimate that the device is about 70% effective at detecting cancer cells, but “they hope to increase both the accuracy and sensitivity of the method by using worms that were previously exposed to cancer cell media and therefore have a ‘memory’ of cancer-specific odor molecules,” according to the statement from the American Chemical Society.

Since C. elegans is easy to grow in a lab and, apparently, easy to train, the researchers hope that the worm-on-a-chip can become a quick, easy, economical, and noninvasive cancer screen.

So watch out cancer, because we never bet against the creepy crawlies.
 

Mosquitoes have us figured out

We are nearing mosquito season; quite possibly the most annoying and itchy time of the year. We stock up on bottles of bug spray, but somehow we still get bite after bite. It appears that mosquitoes are basically able to ignore our bug sprays, which explains why we’re still covered in bites after the Fourth of July fireworks. It turns out mosquitoes are more complex than we thought for such tiny creatures.

Courtesy Jim Gathany/CDC

There’s plenty of research on the best ways to keep mosquitoes away, because not only are they incredibly annoying, but they also carry potentially harmful diseases. In a recent experiment, researchers used mosquitoes that were genetically modified to have an excessive amount of an odor receptor called AgOR2, which responds to the smell of humans.

“AgOR2 overexpression threw a wrench in the whole system by inactivating olfactory receptors in these mosquitoes,” Christopher Potter, PhD, associate professor of neuroscience at Johns Hopkins University, said in a written statement.

After testing how these genetically modified mosquitoes reacted to some of the common smells of bug spray such as lemongrass, they discovered that it’s easy for the mosquitoes to ignore the smell. We wish it were that easy for us to ignore that chemically fruity smell.

Researchers continue to work hard to figure out how to repel mosquitoes and we’re rooting for them as summer approaches, despite the mosquito’s status as a creepy crawly.