Clinician Reviews

Spectacular progress is being made in slowing down aging, with three new molecular indicators of measurable and manageable processes that accelerate or slow down deterioration associated with age, as well as age-related pathologies. These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.

An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.

A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.

María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
 

Eighty experimental interventions

The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.

They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
 

Nutrient sensors

Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.

“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
 

Diet and disease

Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”

Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”

Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.

“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
 

Aging indicators

The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.

“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.

A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”

The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
 

Food fact and fiction

Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”

Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”

Sugars and meat

“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.

“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.

“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.

Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.

Dr. Gómez has disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Spectacular progress is being made in slowing down aging, with three new molecular indicators of measurable and manageable processes that accelerate or slow down deterioration associated with age, as well as age-related pathologies. These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.

An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.

A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.

María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
 

Eighty experimental interventions

The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.

They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
 

Nutrient sensors

Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.

“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
 

Diet and disease

Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”

Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”

Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.

“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
 

Aging indicators

The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.

“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.

A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”

The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
 

Food fact and fiction

Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”

Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”

Sugars and meat

“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.

“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.

“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.

Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.

Dr. Gómez has disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Spectacular progress is being made in slowing down aging, with three new molecular indicators of measurable and manageable processes that accelerate or slow down deterioration associated with age, as well as age-related pathologies. These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.

An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.

A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.

María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
 

Eighty experimental interventions

The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.

They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
 

Nutrient sensors

Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.

“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
 

Diet and disease

Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”

Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”

Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.

“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
 

Aging indicators

The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.

“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.

A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”

The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
 

Food fact and fiction

Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”

Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”

Sugars and meat

“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.

“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.

“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.

Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.

Dr. Gómez has disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Regular use of over-the-counter laxatives has been tied to a significantly increased risk of dementia, particularly among those who use multiple types of laxatives or osmotic laxatives.

Among more than 500,000 middle-aged or older adults in the UK Biobank, those who reported regular laxative use had a 51% increased risk of dementia due to any cause, compared with their counterparts who did not regularly use laxatives.

Individuals who used only osmotic laxatives had a 64% increased risk, compared with peers who did not use laxatives, while those using one or more types of laxatives, including bulk-forming, stool-softening, or stimulating laxatives, had a 90% increased risk.

“Constipation and laxative use are common among middle-aged and older adults,” study investigator Feng Sha, PhD, with the Chinese Academy of Sciences in Guangdong, China, said in a news release.

“However, regular laxative use may change the microbiome of the gut, possibly affecting nerve signaling from the gut to the brain or increasing the production of intestinal toxins that may affect the brain,” Dr. Sha noted.

The study was published online in Neurology.
 

Robust link

The findings are based on 502,229 people (54% women; mean age, 57 at baseline) from the UK biobank database. All were dementia-free at baseline.

A total of 18,235 participants (3.6%) said they used over-the-counter laxatives regularly, which was defined as using them most days of the week during the month before the study.

Over an average of 9.8 years, dementia was recorded in 218 (1.3%) of those who regularly used laxatives and in 1,969 (0.4%) of those did not.

After adjusting for factors such as age, sex, education, other illnesses, medication use, and a family history of dementia, regular use of laxatives was significantly associated with increased risk of all-cause dementia (adjusted hazard ratio, 1.51; 95% confidence interval, 1.30-1.75) and vascular dementia (aHR, 1.65; 95% CI, 1.21-2.27), with no significant association observed for Alzheimer’s disease (aHR, 1.05; 95% CI, 0.79-1.40).

The risk of dementia also increased with the number of laxative types used. All-cause dementia risk increased by 28% (aHR, 1.28; 95% CI, 1.03-1.61) for those using a single laxative type and by 90% (aHR, 1.90; 95% CI, 1.20-3.01) for those using two or more types, compared with nonuse.

Among those who reported using only one type of laxative, only those using osmotic laxatives had a statistically significant higher risk of all-cause dementia (aHR, 1.64; 95% CI, 1.20-2.24) and vascular dementia (aHR, 1.97; 95% CI, 1.04-3.75).

“These results remained robust in various subgroup and sensitivity analyses,” the investigators report.

They caution that they had no data on laxative dosage and so they were unable to explore the relationship between various laxative dosages and dementia risk.
 

Interpret with caution

Commenting on the findings for this news organization, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, said the results are “interesting and demonstrate an association between laxative use and later life risk of dementia.”

However, “there is no proven causation, and there are some caveats,” Dr. Snyder said. “It’s unclear what may be driving this association, though other lines of research have suggested a linkage between our overall gut health, our immune system, and our brain health.”

Dr. Snyder said it’s also worth noting that the data came from the UK Biobank, which, “while a wealth of information for research purposes, is not representative of other countries. More research is needed.”

The Alzheimer’s Association is leading a 2-year clinical trial, U.S. Pointer, to examine the impact of behavioral interventions on the gut-brain axis to “better understand how our gut health may affect our brains,” Dr. Snyder told this news organization.

“While we await the results of that study, people should talk to their doctor about the risks and benefits of laxatives for their health, as well as discuss alternative methods of alleviating constipation, such as increasing dietary fiber and drinking more water,” she advised.

The study was funded by the National Natural Science Foundation of China, Shenzhen Science and Technology Program, and the Chinese Academy of Sciences. The authors and Dr. Snyder have disclosed no relevant financial relationships.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Long-acting antiretroviral therapy (ART) for HIV involving injections every 1 or 2 months not only shows noninferiority to a standard daily oral treatment regimen, it also suppresses HIV even in patients who do not already have virologic suppression, as is typically required before initiation, results from two new studies suggest.

Meanwhile, a third study shows early promise of a long-acting ART regimen that could require injections only twice yearly.

“Instead of having the burden of taking a pill every day, patients with HIV can now have these choices of being able to forget about their treatment for up to 2 months at a time,” Moti N. Ramgopal, MD, first author of one of the three studies, said in a press conference at the Conference on Retroviruses and Opportunistic Infections. “My patients tell me that it’s game-changing for them.”
 

First head-to-head comparison

The injectable intramuscular combination of cabotegravir and rilpivirine, administered once every 1 or 2 months, is the first and only long-acting ART to be approved by the Food and Drug Administration for people with HIV. At the meeting, Dr. Ramgopal, from the Midway Immunology and Research Center in Fort Pierce, Fla., reported the results from the first head-to-head study comparing the regimen with the standard daily oral regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/FTC/TAF).

For the phase 3b SOLAR trial, adults with HIV who were already virologically suppressed and treated with daily B/FTC/TAF were randomly assigned to remain on the oral regimen (n = 223) or switch to the long-acting injections every 2 months, either with an oral lead-in (n = 173) or without a lead-in (n = 274).

The results after 12 months showed noninferiority between the groups, with 90% of the long-acting ART group and 93% in the oral daily pill group maintaining viral suppression, defined as plasma HIV-1 RNA less than 50 copies/mL.

Two patients (0.4%) receiving the long-acting ART in a modified-intention to treat and 3 (0.6%) in the intention-to-treat populations had confirmed virologic failure, and rates of adverse events leading to withdrawal were 6% with the long-acting ART group versus 1% with the oral treatment group.

As many as 90% of subjects reported preferring the long-acting ART over their previous oral therapy at the end of the study, and those in the long-acting group also reported significantly greater improvements in quality of life on the HIV Treatment Satisfaction Questionnaire status version compared with the oral therapy group at the end of the study (P < .001).

Prior to the randomization, as many as 47% of patients on the oral regimen reported “always” or “often” having psychosocial challenges with the daily therapy, including worries of having their HIV status revealed and forgetting to take the medication.

“These data demonstrate that [the long-acting regimen] addresses important unmet needs for people with HIV who are virally suppressed on oral daily HIV therapy, while improving the quality of life,” said Dr. Ramgopal.
 

Suppression at onset not necessarily required

For all of its benefits, a key caveat of the cabotegravir and rilpivirine long-acting regimen is that it is approved only for patients who have already achieved viral suppression and are currently on oral ART, meaning some of the people most in need, including those with unstable housing, mental illness, or substance abuse disorders, may be excluded.

To evaluate the therapy’s efficacy among those patient types, Monica Gandhi, MD, MPH, professor of medicine and associate division chief at the University of California, San Francisco, enrolled 133 participants between June 2021 and November 2022 at the Ward 86 HIV Clinic, a safety-net clinic in San Francisco, to initiate long-acting ART. Participants included 57 patients (43%) with untreated or unsuppressed HIV, and 76 who were virally suppressed on oral ART.

Of the whole study group, 66% reported unstable housing, 8% reported experiencing homelessness, 38% reported having a mental illness, and 33% reported substance use.

Although all of the subjects (100%) who started with viral suppression remained suppressed over the study’s 26-week follow-up, the rate of viral suppression at the study’s end was nearly as high – 55 of 57 subjects (96.5%) – among those who started long-acting ART without having viral suppression.

Of note, the overall rate of study participants who did not achieve or maintain viral suppression (1.5%) was consistent with rates reported in clinical trials of long-acting ART in people with HIV who had previously achieved viral suppression on daily oral ART.

“Our patient population does not look like the patient population that got enrolled in the clinical trials to determine the approval criteria for long-acting ART,” Dr. Gandhi said in presenting the findings.

“If 10% of the population carries 90% of the HIV virus – which we see in modeling – then we need innovations for this population if we want to end the HIV epidemic,” she added.

“We tried long-acting ART in our diverse, urban, low-income population and we saw very high virologic suppression rates equal to those that were seen in the clinical trials,” Dr. Ghandi reported. “This shows that long-acting ART, used creatively and used boldly, could really make a dent in the [efforts] to end the HIV epidemic movement.”

Commenting on the study in a press statement, Nora Volkow, MD, director of the National Institute on Drug Abuse, said “Dr. Gandhi and her team have made state-of-the-art HIV treatment finally available to people with unique challenges, like those who use drugs, and have found success.”

“This is the sweet spot for addressing HIV – thinking outside the box to deliver care in a way that meets people’s needs, even when that means it happens outside the clinic walls, by phone, or on neighborhood streets,” she said. “This can be done, but it requires creativity and resolve.”
 

Twice-yearly dosing option?

Looking ahead, an even more intriguing scenario of a long-acting ART requiring injections only once every 6 months may be getting closer to fruition. Researchers at CROI 2023 reported early but promising safety and efficacy results of an innovative combination of the first-in-class HIV-1 capsid inhibitor lenacapavir with teropavimab and zinlirvimab, two broadly neutralizing antibodies (bNAbs).

To achieve the goal of the longer-acting therapy, Joseph J. Eron, MD, of the University of North Carolina at Chapel Hill, and colleagues modified both antibodies to extend their half-lives and allow less-frequent dosing.

For the phase 1b trial, 20 adult patients with virologically suppressed HIV for at least 18 months were randomly assigned to one of two doses of the ART, both groups receiving lenacapavir at 927 mg subcutaneous after oral loading, plus teropavimab (30 mg/kg IV) and zinlirvimab at either 10 mg/kg or 30 mg/kg.

Patients had to have a CD4 count greater than 500 and CD4 nadir greater than 350, and importantly, patients had to demonstrate sensitivity on DNA phenotyping to both bNAbs at baseline.

After 26 weeks, 18 of the 20 participants (90%) maintained a viral suppression of HIV-1 RNA less than 50 copies/mL.

Of the remaining two patients, one in the 10–mg/kg zinlirvimab group had a confirmed HIV RNA of 50 c/mL (155 copies/mL, confirmed 524 copies/mL) at week 16 and was able to be resuppressed with reinitiation of baseline ART, and one participant in the zinlirvimab 30 mg/kg group withdrew consent at week 12, with viral suppression, and chose to go back on oral therapy

The safety profile looked favorable, with no serious adverse events and two patients with grade 3 AEs, including one experiencing an injection site cellulitis and one with injection site erythema.

Dr. Eron noted that “bNAb sensitivity is an important issue and a limitation for broad use, [because] only about 50% of people with HIV in the U.S. would be sensitive to both antibodies.”

However, “we are doing a pilot of only 10 participants looking to see if it works with sensitivity to a single antibody, which would increase [applicability] to about 90% of people with HIV,” he said in an interview.

At a press conference, Dr. Eron commented on how far HIV treatment has come, from the early days of patients having to wake up every 4 hours to take their medication, then to having to take 15-20 pills a day, to the current option of long-acting ART every other month, and now the potential of just a twice-yearly treatment.

“This is a very preliminary proof-of-concept study and not a very large study, but I think it’s incredibly important,” he said.

The SOLAR study was funded by ViiV Healthcare. Dr. Ramgopal has received speaking and/or consulting fees from AbbVie, Gilead Sciences, Janssen, Merck, and ViiV Healthcare. Dr. Eron’s study was funded by Gilead Sciences.

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

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

Irregular sleep – such as inconsistent sleep duration or sleep timing – may increase the risk of developing atherosclerosis among adults older than age 45, a new report suggests.

In particular, variation in sleep duration of more than 2 hours per night in the same week was tied to higher rates of atherosclerosis.

“Poor sleep is linked with several cardiovascular conditions, including heart disease, hypertension, and type 2 diabetes,” lead author Kelsie M. Full, PhD, MPH, assistant professor of medicine at Vanderbilt University Medical Center, Nashville, Tenn., said in an interview.

“Overall, we found that participants who slept varying amounts of hours throughout the week (meaning that one night they slept less, one night they slept more) were more likely to have atherosclerosis than participants who slept about the same amount of time each night,” she said.

The study was published online in the Journal of the American Heart Association.
 

Analyzing associations

Dr. Full and colleagues examined data from 2032 participants in the Multi-Ethnic Study of Atherosclerosis Sleep Ancillary Study, which included adults aged between 45 and 84 years in six U.S. communities who completed 7-day wrist actigraphy assessment and kept a sleep diary between 2010 and 2013.

For subclinical markers of cardiovascular disease, participants underwent assessments of coronary artery calcium, carotid plaque presence, carotid intima-media thickness, and ankle-brachial index.

The research team assessed sleep duration, or the total number of minutes of sleep in a night, and sleep timing regularity, which was determined on the basis of the time someone initially fell asleep each night. They adjusted for cardiovascular disease risk factors and sleep characteristics, such as obstructive sleep apnea, sleep duration, and sleep fragmentation.

The average age of the participants was 68.6 years, and 53.6% were women. About 37.9% identified as White, 27.6% as Black or African American, 23.4% as Hispanic American, and 11.1% as Chinese American.

During the 7-day period, about 38% of participants experienced a change in sleep duration of more than 90 minutes, and 18% experienced a sleep duration change of more than 120 minutes. Those who had irregular sleep were more likely to be non-White, current smokers, have lower average annual incomes, have work shift schedules or did not work, and have a higher average body mass index.

For the study, sleep duration irregularity was defined as a standard deviation of more than 120 minutes. Those participants who had a greater degree of sleep irregularity were more likely to have high coronary artery calcium burden than those whose sleep duration was more more regular, defined as an SD of 60 minutes or less (> 300; prevalence ratio, 1.33; 95% confidence interval, 1.03-1.71), as well as abnormal ankle-brachial index (< 0.9, prevalence ratio, 1.75;95% CI, 1.03-2.95).

Further, those with irregular sleep timing (SD > 90 minutes) were more likely to have a high coronary artery calcium burden (prevalence ratio, 1.39; 95% CI, 1.07-1.82) in comparison with those with more regular sleep timing (SD < 30 minutes).

“The biggest surprise to me was that 30% of the participants in the study had total sleep times that varied by more than 90 minutes over the course of the week,” Dr. Full said. “This is consistent with prior studies that suggest that a large proportion of the general public have irregular sleep patterns, not just shift workers.”
 

Investigating next steps

In additional analyses, Dr. Full and colleagues found that sleep duration regularity continued to be associated with high coronary artery calcium burden and abnormal ankle-brachial index when accounting for severe obstructive sleep apnea, average nightly sleep duration, and average sleep fragmentation.

Notably, when sleep duration was added, all participants with more irregular sleep durations (SD > 60 minutes) were more likely to have a high coronary artery calcium burden, compared with those with regular sleep durations (SD < 60 minutes). The results remained when participants who reported shift work, including night shift work, were excluded.

Additional studies are needed to understand the mechanisms, the study authors wrote. Night-to-night variability in sleep duration and sleep timing can cause desynchronization in the sleep-wake timing and circadian disruption.

“A key issue highlighted in this study is that sleep irregularity itself, independent of how much sleep people were getting, was related to heart health. Sleep is a naturally recurring phenomenon, and maintaining regularity helps provide stability and predictability to the body,” Michael Grandner, PhD, associate professor of psychiatry and director of the sleep and health research program at the University of Arizona, Tucson, said in an interview.

Dr. Grandner, who wasn’t involved with this study, has researched sleep irregularity and associations with cardiovascular disease, diabetes, obesity, and many other adverse outcomes.

“When people have very irregular sleep schedules, it may make it harder for the body to optimally make good use of the sleep it is getting, since it such a moving target,” he said. “The unique angle here is the ability to focus on regularity of sleep.”

The study was supported by the National Heart, Lung, and Blood Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health. One author received grants and consulting fees from pharmaceutical companies unrelated to the research. The other authors and Dr. Grandner disclosed no relevant financial relationships.

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

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

An investigational smartphone app that delivers cognitive behavioral therapy (CBT) to people with type 2 diabetes led to a significant 10 percentage point cut in the incidence of antihyperglycemic-drug intensification during 6 months’ follow-up, when compared with a control phone app, in the CBT app’s pivotal trial with 669 randomized patients.

Previously reported results from this trial, called BT-001, showed that people randomized to use the CBT app had a significant average 0.4 percentage point reduction in hemoglobin A1c, compared with controls, after 90 days for the trial’s primary endpoint, and a significant 0.29 percentage point reduction in A1c, compared with controls, after 180 days.

The new finding, that these incremental drops in A1c occurred while the control patients also received significantly more intensification of their antihyperglycemic medication, provides further evidence for the efficacy of the CBT app, said Marc P. Bonaca, MD, in a press conference organized by the American College of Cardiology in advance of its upcoming joint scientific sessions.

The CBT app “significantly reduced A1c despite less intensification of antihyperglycemic therapy,” noted Dr. Bonaca, a vascular medicine specialist and executive director of CPC Clinical Research, an academic research organization created by and affiliated with the University of Colorado at Denver, Aurora.

Based on positive safety and efficacy findings from the primary-endpoint phase of the BT-001 trial, reported in Diabetes Care, the company developing the CBT app, Better Therapeutics, said in a statement that the U.S. Food and Drug Administration accepted the company’s application for de novo classification and marketing approval of the app, also called BT-001. If the agency grants this classification and marketing approval, the company plans to sell the app on a prescription basis for use by people with type 2 diabetes.


 

CBT app gives patients problem-solving skills

CBT gives people with type 2 diabetes a way to better understand their unhelpful behaviors and motivations and teaches them problem-solving skills. Providing this counseling via an app addresses the challenge of making the intervention scalable to a broad range of patients, Dr. Bonaca explained.

“Clinicians are frustrated by trying to produce behavioral change” in patients. The BT-001 app “provides a new avenue to treatment,” an approach that clinicians have been “very receptive” to using “once they understand the mechanism,” Dr. Bonaca said during the press conference. “The effect at 90 days was very similar to what a drug would do. It’s not just drugs any more” for treating people with type 2 diabetes, he declared.

“CBT is an empirically supported psychotherapy for a variety of emotional disorders, and it has been adapted to target specific emotional distress in the context of chronic illness,” commented Amit Shapira, PhD, a clinical psychologist at the Joslin Diabetes Center in Boston who has not been involved in the BT-001 studies. A CBT protocol designed for diabetes, CBT for Adherence and Depression “has been shown to have a positive impact on depression symptoms and glycemic control in adults with type 2 diabetes,” Dr. Shapira noted in an interview.

“Once a physician explains this [CBT] app and patients understand how to use it, then patients will be happy to use it,” commented Julia Grapsa, MD, PhD, a cardiologist at St. Thomas Hospital in London, who moderated the press conference. “We may see an explosion of apps like this one, designed to help better control” other chronic disorders, such as elevated blood pressure or abnormal lipid levels, Dr. Grapsa predicted. “I’m very optimistic that these apps have a great future in health care.”
 

Forty percent relative cut in new antihyperglycemic drug use

The BT-001 study randomized 669 adults with smartphone access and type 2 diabetes at any of six U.S. sites. The enrolled patients had type 2 diabetes for an average of 11 years, and an A1c of 7%-10.9% with an average level of 8.2%. Participants had to be on a stable medication regimen for at least 3 months but not using prandial insulin, and their treatment regimens could undergo adjustment during the trial. At baseline, each subject was on an average of 2.1 antihyperglycemic medications, including 90% on metformin and 42% on a sulfonylurea.

The new results reported by Dr. Bonaca showed that, during follow-up, people using the app had a 14.4% rate of antihyperglycemic drug intensification compared with a 24.4% rate among the controls, a roughly 40% relative decrease in new antihyperglycemic medication use. In addition, among those using insulin at baseline, 3.8% of controls increased their insulin dose, compared with 1.5% of those using the CBT app, while insulin doses decreased in 0.9% of the control subjects and in 2.2% of those using the BT-001 app.

Further study findings, first reported by Dr. Bonaca at the American Heart Association scientific sessions in late 2022, also showed a clear dose-response pattern for the CBT app: the more CBT lessons a person completed, the greater their reduction in A1c over 180 days of app use. People who used the app fewer than 10 times had an average reduction from baseline in their A1c of less than 0.1 percentage points. Among those who used the app 10-20 times (a subgroup with roughly one-third of the people randomized to app use), average A1c reduction increased to about 0.4 percentage points, and among those who used the app more than 20 times (also about one-third of the intervention group), the average A1c reduction from baseline was about 0.6 percentage points.

“It would be interesting to learn more about the adults who engaged with the app” and had a higher use rate “to provide more targeted care” with the app to people who match the profiles of those who were more likely to use the app during the trial, said Dr. Shapira.

This “clear” dose-response relationship “was one of the most exciting findings. It helps validate the mechanism,” Dr. Bonaca said during the press conference. “We’re now modeling which patients were the most engaged” with using the app, and “looking at ways to increase app engagement.”

Better Therapeutics also announced, in December 2022, results from a separate, uncontrolled study of a similar CBT app in 19 people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. The findings showed that use of the tested app linked with an average 16% drop from baseline in liver fat content as measured by MRI, as well as other improvements in markers of hepatic function. The company said in a statement that based on these findings it planned to apply for breakthrough-device designation with the FDA for use of a liver-specific CBT app in people with nonalcoholic fatty liver disease and nonalcoholic steatohepatitis.

The BT-001 trial was sponsored by Better Therapeutics, the company developing the app. CPC Clinical Research receives research and consulting funding from numerous companies. Dr. Bonaca has been a consultant to Audentes, and is a stockholder of Medtronic and Pfizer. Dr. Shapira and Dr. Grapsa had no disclosures.

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

The benefits of doxycycline postexposure prophylaxis (Doxy PEP) in preventing the transmission of sexually transmitted infections (STIs) in men and transgender women do not appear to extend to cisgender women, who have disproportionately high rates of infection in many regions.

“This was the first trial to evaluate doxycycline PEP for cisgender women,” said first author Jenell Stewart, DO, of the University of Minnesota, Minneapolis, in discussing the findings at a press conference at the Conference on Retroviruses & Opportunistic Infections.

“Unfortunately, our primary outcome was not statistically significant – we did not see a reduction in STIs among cisgender women, which is in stark contrast to [reported effects] among cisgender men and transgender women,” she said.

The findings are from a study of 449 nonpregnant cisgender women (mean age, 24 years) in Kenya who had been taking daily oral HIV preexposure prophylaxis (PrEP) for a median of about 7 months.

The women were randomly assigned to receive either Doxy PEP 200 mg, to be taken within 72 hours of sex (n = 224), or standard care, which included quarterly screening and treatment of STIs (n = 225).

Of the women, 36.7% reported transactional sex at enrollment; their baseline prevalence of STIs was 17.9%, including 14.1% with chlamydia, 3.8% gonorrhea, and 0.4% syphilis. There were no differences between the study groups.

In surveys, 78% of the women reported adherence to the use of Doxy PEP; they took the prophylaxis at least as many days as they had sex.

Nevertheless, there was no significant difference in the incidence of STIs, reported over 1 year, at quarterly visits that included genital STI testing, between groups, with 50 patients in the Doxy PEP group and 59 in the standard screening group developing STIs (relative risk, 0.88; P = .51).

Of the infections, 85 were chlamydia, including 35 in the Doxy PEP group and 50 with standard of care, while 31 were gonorrhea, including 19 in the Doxy PEP group and 12 with standard of care; 8 had both infections, and there was 1 syphilis infection.

The results were consistent across subanalyses of patients grouped according to STI, who became pregnant (n = 80), or sorted by other factors including age, contraceptive use, transactional sex, and STI at baseline.

None of the women developed HIV, and there were no serious events associated with the Doxy PEP treatment.
 

Cisgender women bear ‘highest burden’ of STIs

The findings are disappointing in light of the higher rates of STIs among cisgender women, with the Centers for Disease Control and Prevention reporting that women also disproportionately bear the long-term consequences of STIs.

“For example, each year, untreated sexually transmitted diseases cause infertility in at least 20,000 women in the United States, and a pregnant woman is highly likely to pass syphilis unto her unborn baby if left untested or untreated,” the CDC reports.

The STI rates are particularly high for women taking HIV PrEP in regions like East Africa, where rates of STIs among cisgender women in many cases are higher than rates for men taking PrEP in high income countries, Dr. Stewart said.

Previous studies of Doxy PEP in men and transgender women taking HIV PrEP, including new research presented at CROI, have shown highly encouraging reductions in STIs, at rates of up to approximately 80% for chlamydia and syphilis.
 

Adherence, anatomy, resistance

The key theories for the lack of a prevention of infections in cisgender women surround the issues of resistances, as well as anatomy and adherence, said Dr. Stewart.

In terms of bacterial resistances, while initial testing in a limited number of samples the study found no evidence of markers of resistance for chlamydia, all of the gonorrhea samples did show tetracycline-resistant N gonorrhea at baseline and follow-up in both groups.

Regarding anatomic differences, doxycycline may not prevent STIs in endocervical tissue among cisgender women, Dr. Stewart noted. Women are known to be at higher risk of infection because the lining of the vagina is thinner than the skin of the penis, allowing for easier penetration of bacteria and viruses.

The study was designed to optimize adherence to Doxy PEP. Measures included monitoring with weekly text message surveys, in which the women reported a high rate of adherence.

The overall retention rate in the study was high; as many as 97% of the quarterly follow-up visits were completed, including 95% in the Doxy PEP group and 98% of the standard care group. The response rate for the weekly surveys was 81%.

Of note, women reported the use of the treatment to be “imperfect,” suggesting social problems, such as biases toward the use of the prophylaxis.

The results underscore the need for ongoing efforts to make sure no groups of patients are left behind as interventions advance, Dr. Stewart said.

“The burden of STIs on cisgender women is large and growing,” she concluded. “STI prevention interventions are needed.”

Commenting on the study, Renee A. Heffron, PhD, MPH, said the findings “are somewhat surprising because results from trials in other populations have been positive.

“But cisgender women are exposed through the cervix, and this tissue is different from rectal or urethral tissue,” Dr. Heffron, a professor at the department of medicine and director of the Center for AIDS Research at the University of Alabama, Birmingham, told this news organization.

Further findings from the research should help shed light on key issues of adherence and drug concentration levels in cervical tissue, she added.

“For cisgender women, these data are the first and the beginning of understanding whether this is a viable strategy,” Dr. Heffron said.

“We have more to learn to better understand the results from the trial main outcomes, and if there are tweaks to this strategy that would improve efficacy.”

The authors and Dr. Heffron have disclosed no relevant financial relationships.

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

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

HONOLULU – In the clinical experience of April W. Armstrong, MD, MPH, topical therapies typically don’t work well for nail psoriasis, so she sometimes resorts to intralesional injections combined with systemic therapy.

One might think of intralesional injections “as a torture method from the medieval days,” she said at the Hawaii Dermatology Seminar provided by MedscapeLIVE!, but intramatricial corticosteroid injections have been performed for many years as a treatment for nail psoriasis, typically with triamcinolone acetonide.

Doug Brunk/MDedge News

According to Dr. Armstrong, professor of dermatology and associate dean of clinical research at the University of Southern California, Los Angeles, nail matrix psoriasis can present as pitting, leukonychia, red macules in the lunula, crumbling, or trachyonychia. Nail bed psoriasis can present as splinter hemorrhages and onycholysis, hyperkeratosis and splinter hemorrhages, salmon patch or oil spot dyschromia, or onycholysis and salmon patch dyschromia.

In a German cross-sectional study of patients with psoriasis, nails were one of the body sites that have the greatest impact on quality of life – especially those in younger age groups.

While topical treatments are generally considered first for limited disease involving special areas such as the nails, systemic therapy is warranted in patients with moderate-to-severe involvement of specific sites or in those refractory to topical therapy, Dr. Armstrong said.

In 2018, Indian researchers published results from an open-label study of 17 patients, with nail psoriasis, comparing three treatments . Patients were assigned to three groups of 30 nails each and treated with intramatricial injections of triamcinolone acetonide (10 mg/mL), methotrexate (25 mg/mL), and cyclosporine (50 mg/mL), respectively. Each nail was treated with two injections at 6-week intervals and graded at 24 weeks using the Nail Psoriasis Severity Index (NAPSI). In the triamcinolone acetonide and methotrexate groups, 50% of treated nails showed a greater than 75% improvement at 24 weeks, compared with 33% of those in the cyclosporine group. The most side effects occurred in the nails treated with cyclosporine.

When Dr. Armstrong performs intramatricial injections, she uses triamcinolone acetonide at 10 mg/mL. However, she said, “my favorite way of treating severe nail psoriasis is with biologics.”

In an early study of patients with moderate to severe psoriasis treated with the tumor necrosis factor blocker adalimumab 80 mg subcutaneously at week 0, followed by 40 mg subcutaneously every other week from weeks 1 to 15, a post hoc analysis on the effects on nail psoriasis showed a 10-point decrease in the median NAPSI score through week 16 – from 21 to 11 .

In VOYAGE 2, which compared the interleukin-23 blocker guselkumab and adalimumab in patients with moderate to severe psoriasis, the mean percent improvement from baseline in the NAPSI score was similar in patients treated with adalimumab or guselkumab at week 16 (39.6% vs. 46.9%, respectively) and at week 24 (55% vs. 53.7%).

In another study of patients with nail psoriasis, researchers evaluated the efficacy of the IL-17A antagonist secukinumab 150 mg, 300 mg, or placebo at weeks 0, 1, 2, 3, and 4, and every 4 weeks thereafter for 2.5 years. At 2.5 years, the mean reduction in NAPSI score was 63.6% in the secukinumab 150 mg group and 73.3% in the secukinumab 300 mg group.

“I do have to tell my patients what to expect, because the nails grow out slowly, but over time we do see this increase in efficacy,” Dr. Armstrong said.

Studies of another IL-17A antagonist, ixekizumab, have yielded positive results as well, she noted. In 2021, Taiwanese researchers published a systematic review and network meta-analysis to evaluate the efficacy of small molecule inhibitors and biologics in treating nail psoriasis. They drew from 39 studies involving 15,673 patients with nail psoriasis and found that the oral Janus kinase inhibitor tofacitinib and ixekizumab had the best efficacy for treating nail psoriasis in 10-16 weeks and 24-26 weeks, respectively.

“They found that overall, the biologics have a good effect on nail psoriasis and that the treatment effects are overall quite similar,” Dr. Armstrong said.

Dr. Armstrong disclosed that she is a consultant or adviser for numerous pharmaceutical companies. She has also received research funding from Bristol-Myers Squibb, Dermavant, Dermira, Leo, Lilly, Pfizer, and UCB Pharma.

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

Prone positioning significantly reduced the need for intubation among nonintubated adults with COVID-19, as indicated by data from a new meta-analysis of more than 2,000 individuals.

The use of prone positioning for nonintubated patients (so-called “awake prone positioning”) has been common since the early days of the COVID-19 pandemic. Prone positioning is more comfortable for patients, and it entails no additional cost. Also, awake prone positioning is less labor intensive than prone positioning for intubated patients, said Jie Li, PhD, in a presentation at the Critical Care Congress sponsored by the Society of Critical Care Medicine.

However, data on the specific benefits of prone positioning are lacking and contradictory, said Dr. Li, a respiratory care specialist at Rush University, Chicago.

Dr. Li and colleagues from a multinational research group found that outcomes were improved for patients who were treated with awake prone positioning – notably, fewer treatment failures at day 28 – but a pair of subsequent studies by other researchers showed contradictory outcomes.

For more definitive evidence, Dr. Li and colleagues conducted a systematic review and meta-analysis of 11 randomized, controlled trials and one unpublished study of awake prone positioning for patients with COVID-19. The studies were published between Jan. 1, 2020, and July 1, 2022, and included a total of 2,886 adult patients.

The primary outcome was the reported cumulative risk of intubation among nonintubated COVID-19 patients. Secondary outcomes included mortality, the need for escalating respiratory support, length of hospital length of stay, ICU admission, and adverse events.

Overall, awake prone positioning significantly reduced the intubation risk among nonintubated patients compared to standard care (risk ratio, 0.85).

A further subgroup analysis showed a significant reduction in risk for intubation among patients supported by high-flow nasal cannula or noninvasive ventilation (RR, 0.83).

However, no additional reduction in intubation risk occurred among patients who received conventional oxygen therapy (RR, 1.02).

Mortality rates were similar for patients who underwent awake prone positioning and those who underwent supine positioning (RR, 0.96), as was the need for additional respiratory support (RR, 1.03). The length of hospital stay, ICU admission, and adverse events were similar between the patients who underwent prone positioning and those who underwent supine positioning.

The findings were limited by several factors. There was a potential for confounding by disease severity, which may have increased the use of respiratory support devices, Li said in her presentation.

“Another factor we should not ignore is the daily duration of prone positioning,” said Dr. Li. More research is needed to identify which factors play the greatest roles in treatment success.

The current study was important in that it evaluated the current evidence of awake prone positioning, “particularly to identify the patients who benefit most from this treatment, in order to guide clinical practice,” Dr. Li said in an interview.

“Since early in the pandemic, awake prone positioning has been broadly utilized to treat patients with COVID-19,” she said. “In 2021, we published a multinational randomized controlled trial with over 1,100 patients enrolled and reported lower treatment failure. However, no significant differences of treatment failure were reported in several subsequent multicenter randomized, controlled trials published after our study.”

Dr. Li said she was not surprised by the findings, which reflect those of her team’s previously published meta-analysis. “The increased number of patients helps confirm our previous finding, even with the inclusion of several recently published randomized controlled trials,” she said.

For clinicians, “the current evidence supports the use of awake prone positioning for patients with COVID-19, particularly those who require advanced respiratory support from high-flow nasal cannula or noninvasive ventilation,” Dr. Li said.

The study received no outside funding. Dr. Li has relationships with AARC, Heyer, Aeorgen, the Rice Foundation, and Fisher & Paykel Healthcare.

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

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

Youth with type 1 diabetes who use real-time continuous glucose monitoring (rtCGM) and an insulin pump spend more time in target glucose range than do those using intermittently scanned CGM (isCGM) and/or multiple daily insulin injections, new data show.

In the multinational cohort study of more than 4,500 people younger than age 21 with type 1 diabetes, those using rtCGM and pumps also spent less time above and below glucose targets and had fewer severe adverse events – either severe hypoglycemia or diabetic ketoacidosis (DKA) – compared with injections and isCGM.

Daria Nipot/Getty Images

The findings were published online in JAMA Network Open by Klemen Dovc, MD, PhD, assistant professor in the department of pediatric endocrinology, diabetes, and metabolic diseases, University Children’s Hospital, Ljubljana, Slovenia, and colleagues.

“These results underscore the synergistic effect of advanced diabetes technologies that should be more readily available to youths with type 1 diabetes for further improvement of diabetes-related clinical outcomes,” the authors wrote.

Moreover, Dr. Dovc told this news organization: “Clinicians should be aware that there may be differences in effectiveness between different types of devices, and that choosing the right device for each individual may be important for achieving optimal outcomes.”
 

Real-time CGM + insulin pump = highest time in range

The researchers explained that two modalities of CGM are broadly available: rtCGM, which continuously displays glucose concentration in the interstitial fluid (usually at intervals of 1-5 minutes) on a dedicated receiver or other portable device, such as a smartphone, and provides various adjustable alarms, and isCGM, which displays data on demand when the transmitter is scanned using either a dedicated reader or smartphone-based application.

rtCGMs include devices from Dexcom and Medtronic. The isCGM, or “flash,” generally refers to the Abbott FreeStyle Libre.

The study included individuals younger than 21 years from 34 centers in 21 countries in the SWEET registry, a worldwide network of diabetes care centers for youth, between Jan. 1, 2016, and Dec. 31, 2021.

The researchers didn’t report which particular devices were used in the trial, rather they just divided patients into four groups: 850 used isCGM with a pump, 1,231 used isCGM with multiple daily injections, 2,252 used rtCGM with a pump, and 886 used rtCGM with insulin injections.

After adjustments for sex, age, diabetes duration, and body mass index standard deviation score, rtCGM plus insulin pump was the most likely group to achieve the recommended greater than 70% time in target glycemic range (70-180 mg/dL), with 36.2% achieving it, followed by rtCGM plus injections, at 20.9%, and isCGM plus injections, at 12.5%. Those using isCGM with an insulin pump were the least likely to achieve time in range, at just 11.3%.

Similar trends were seen for the recommended goal of less than 4% of time spent below range (< 70 mg/dL) and less than 25% of time spent above range (> 180 mg/dL). Those using rtCGM with a pump had the highest proportions achieving both of those goals, 73.1% and 32.5%, respectively.  

The use of rtCGM, with or without a pump, was associated with lower rates of severe hypoglycemia (2.5% and 2.0%, respectively) than isCGM with or without a pump (5.5% and 5.2%, respectively).

Similarly, the proportion experiencing at least one DKA episode varied from 1.4% for rtCGM plus insulin pump and 0.7% for rtCGM plus injections to 3.0% for isCGM plus pump and 1.5% isCGM plus injections.


 

Study looked at older technology but results still reflect benefit

Among the rtCGM plus insulin pump group were 264 participants (5% of the total study population) recorded in the database as using automated insulin delivery (AID) systems, also known as the artificial pancreas, although this is likely an undercount as the presence of communication between the two devices was not automatically recorded, Dr. Dovc explained.

Those individuals recorded as using AIDs had a higher unadjusted time in range compared with non-AID users (66.3% vs. 59.0%) and lower time above range (30.1% vs. 37.0%) but didn’t differ in time below range (2.9% vs. 3.0%).

Dr. Dovc told this news organization: “While automated systems are becoming more common, there are still many individuals who do not have access to glucose-responsive devices.” Reasons include lack of reimbursement, or decisions not to use them, he said.

But, he added, “Despite the low reported numbers of AID users, results achieved in the pump with real-time CGM [group] are admirable and approaching recommended consensus targets with a clinically meaningful difference towards all other treatment modalities. As our findings may not be directly applicable to all participants using automated systems, they may still provide useful insights into the factors that influence glycemic control.”

Similarly, the intermittently scanned CGMs used by most in the study, and particularly in the earlier period, didn’t have low- or high-glucose alarms as do later versions. And an even more recent version also doesn’t require scanning either, so is essentially also “real-time.”

Dr. Dovc noted, “in the first half of our observational period only first generation of intermittently-scanned CGM was generally available, and we can speculate that only a small proportion started to use second generation towards the end of our observational period. The exact number of second-generation users was not available in this analysis.”

He acknowledged that because the study was observational and not randomized, patient choice of device could have influenced the outcomes.

“For example, participants who choose to use a more expensive device may have more resources or support available to them, which could influence their ability to manage their diabetes effectively. Additionally, individuals who choose to use a particular device may be more motivated or engaged in their diabetes care, which could also impact their outcomes. It would be important for future studies to explore the impact of device selection on device effectiveness and to control for this potential confounding factor in the analysis.”

This study was supported by the international Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) corporate members, including Abbott Laboratories, Boehringer Ingelheim, Dexcom, Insulet, Eli Lilly, Medtronic, Sanofi, and the Slovenian National Research Agency. Dr. Dovc disclosed ties with Abbott Laboratories, Medtronic, Novo Nordisk, Eli Lilly, and Pfizer. He served as a member of the European Commission Expert Panel for Medical Devices for Endocrinology and Diabetes.   

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

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

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

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

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

Drinking two or more cups of coffee a day was associated with twice the risk of death from cardiovascular disease among people with severe hypertension, according to researchers at Institute for Global Health Policy Research, Bureau of International Health Cooperation, National Center for Global Health and Medicine, Tokyo.

What to know

People with severely high blood pressure who drink two or more cups of caffeinated coffee each day could double their risk of dying from a heart attack, stroke, or any type of cardiovascular disease.

Too much coffee may raise blood pressure and lead to anxiety, heart palpitations, and difficulty sleeping.

An 8-ounce cup of coffee has 80-100 mg of caffeine, while an 8-ounce cup of green or black tea has 30-50 mg.

Drinking one cup of coffee a day or any amount of green tea was not associated with risk of death across any blood pressure categories, and drinking green tea was not associated with increased risk of death related to cardiovascular disease at any blood pressure level.

Frequent consumers of coffee were more likely to be younger, current smokers, current drinkers, to eat fewer vegetables, and to have higher total cholesterol levels and lower systolic blood pressure regardless of their blood pressure category.

This is a summary of the article “Coffee and Green Tea Consumption and Cardiovascular Disease Mortality Among People With and Without Hypertension,” published in the Journal of the American Heart Association.

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