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Toxic chemicals we consume without knowing it
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Life expectancy is falling precipitously. Three-fourths of Americans are overweight or obese, half have diabetes or prediabetes, and a majority are metabolically unhealthy. Furthermore, the rates of allergic, inflammatory, and autoimmune diseases are rising at rates of 3%-9% per year in the West, far faster than the speed of genetic change in this population.
Of course, diet and lifestyle are major factors behind such trends, but a grossly underappreciated driver in what ails us is the role of environmental toxins and endocrine-disrupting chemicals. In years past, these factors have largely evaded the traditional Western medical establishment; however, mounting evidence now supports their significance in fertility, metabolic health, and cancer.
Although several industrial chemicals and toxins have been identified as carcinogens and have subsequently been regulated, many more remain persistent in the environment and continue to be freely used. It is therefore incumbent upon both the general public and clinicians to be knowledgeable about these exposures. Here, we review some of the most common exposures and the substantial health risks associated with them, along with some general guidance around best practices for how to minimize exposure.
Microplastics
“Microplastics” is a term used to describe small fragments or particles of plastic breakdown or microbeads from household or personal care products, measuring less than 5 mm in length.
Plastic waste is accumulating at alarming and devastating proportions – by 2050, it is estimated that by weight, there will be more plastic than fish in the oceans. That translates into hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.
Since the 1950s, plastic exposure has been shown to promote tumorigenesis in animal studies, and in vitro studies have demonstrated the toxicity of microplastics at the cellular level. However, it is not well known whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins to bioaccumulate.
According to Tasha Stoiber, a senior scientist at the Environmental Working Group, “Microplastics have been widely detected in fish and seafood, as well as other products like bottled water, beer, honey, and tap water.” The EWG states there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment.
Pressure also is mounting for a ban on microbeads in personal care products.
Until such bans are put in place, it is advised to avoid single-use plastics, favor reusable tote bags for grocery shopping rather than plastic bags, and opt for loose leaf tea or paper tea bags rather than mesh-based alternatives.
Phthalates
Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are commonly found in household items such as vinyl (for example, flooring, shower curtains) and fragrances, air fresheners, and perfumes.
Phthalates are known hormone-disrupting chemicals, exposure to which has been associated with abnormal sexual and brain development in children, as well as lower levels of testosterone in men. Exposures are thought to occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that a majority of exposure is probably food related.
To avoid phthalate exposures, recommendations include avoiding polyvinyl chloride plastics (particularly food containers, plastic wrap, and children’s toys), which are identifiable by the recycle code number 3, as well as air fresheners and fragranced products.
The EWG’s Skin Deep database provides an important resource on phthalate-free personal care products.
Despite pressure from consumer advocacy groups, the U.S. Food and Drug Administration has not yet banned phthalates in food packaging.
Bisphenol A (BPA)
BPA is a chemical additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals, with roughly 6 billion pounds produced each year. BPA is traditionally found in many clear plastic bottles and sippy cups, as well as in the lining of canned foods.
Structurally, BPA acts as an estrogen mimetic and has been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements (bisphenol S and bisphenol F) are any safer; they appear to have similar hormonal effects as BPA.
As with phthalates, the majority of ingestion is thought to be food related. BPA has been found in more than 90% of a representative study population in the United States.
Guidance advises avoiding polycarbonate plastics (identifiable with the recycling code number 7), as well as avoiding handling thermal papers such as tickets and receipts, if possible. Food and beverages should be stored in glass or stainless steel. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics, and food and beverages should never be reheated in plastic containers or wrapping. Canned foods should ideally be avoided, particularly canned tunas and condensed soups. If canned products are bought, they should ideally be BPA free.
Dioxins and polychlorinated biphenyls (PCBs)
Dioxins are mainly the byproducts of industrial practices; they are released after incineration, trash burning, and fires. PCBs, which are somewhat structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped in the same category under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.
Tetrachlorodibenzodioxin, perhaps the best-known dioxin, is a known carcinogen. Dioxins also have been associated with a host of health implications in development, immunity, and reproductive and endocrine systems. Higher levels of PCB exposure have also been associated with an increased risk for mortality from cardiovascular disease.
Notably, dioxin emissions have been reduced by 90% since the 1980s, and the U.S. Environmental Protection Agency has banned the use of PCBs in industrial manufacturing since 1979. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.
The best ways to avoid exposures are through limiting meat, fish, and dairy consumption and trimming the skin and fat from meats. The level of dioxins and PCBs found in meat, eggs, fish, and dairy are approximately 5-10 times higher than they are in plant-based foods. Research has shown that farmed salmon is likely to be the most PCB-contaminated protein source in the U.S. diet; however, newer forms of land-based and sustainable aquaculture probably avoid this exposure.
Pesticides
The growth of modern monoculture agriculture in the United States over the past century has coincided with a dramatic surge in the use of industrial pesticides. In fact, over 90% of the U.S. population have pesticides in their urine and blood, regardless of where they live. Exposures are thought to be food related.
Approximately 1 billion pounds of pesticides are used annually in the United States, including nearly 300 million pounds of glyphosate, which has been identified as a probable carcinogen by European agencies. The EPA has not yet reached this conclusion, although the matter is currently being litigated.
A large European prospective cohort trial demonstrated a lower risk for cancer in those with a greater frequency of self-reported organic food consumption. In addition to cancer risk, relatively elevated blood levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality. Also, exposure to DDE – a metabolite of DDT, a chlorinated pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer’s-type dementia as well as overall cognitive decline.
Because these chlorinated pesticides are often fat soluble, they seem to accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH. This has led to the recommendation that consumers of produce should favor organic over conventional, if possible. Here too, the EWG provides an important resource to consumers in the form of shopper guides regarding pesticides in produce.
Per- and polyfluoroalkyl substances (PFAS)
PFAS are a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluoride bond, giving them a persistence within the environment that has led to their being referred to as “forever chemicals.”
PFAS have been detected in the blood of 98% of Americans, and in the rainwater of locations as far afield as Tibet and Antarctica. Even low levels of exposure have been associated with an increased risk for cancer, liver disease, low birth weight, and hormonal disruption.
The properties of PFAS also make them both durable at very high heat and water repellent. Notoriously, the chemical was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick coating of pots and pans. Although perfluorooctanoic acid (PFOA) was removed from nonstick cookware in 2013, PFAS – a family of thousands of synthetic compounds – remain common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products. PFAS are released into the environment during the breakdown of these consumer and industrial products, as well as from dumping from waste facilities.
Alarmingly, the EWG notes that up to 200 million Americans may be exposed to PFAS in their drinking water. In March 2021, the EPA announced that they will be regulating PFAS in drinking water; however, the regulations have not been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.
To avoid or prevent exposures from PFAS, recommendations include filtering tap water with either reverse osmosis or activated carbon filters, as well as avoiding fast food and carry-out food, if possible, and consumer products labeled as “water resistant,” “stain-resistant,” and “nonstick.”
In a testament to how harmful these chemicals are, the EPA recently revised their lifetime health advisories for PFAS, such as PFOA, to 0.004 parts per trillion, which is more than 10,000 times smaller than the previous limit of 70 parts per trillion. The EPA also has proposed formally designating certain PFAS chemicals as “hazardous substances.”
Dr. Goel, clinical assistant professor of medicine at Weill Cornell Medicine, New York, has disclosed no relevant financial relationships. A version of this article originally appeared on Medscape.com.
Irregular sleep tied to markers of atherosclerosis
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.
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.
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.
FROM THE JOURNAL OF THE AMERICAN HEART ASSOCIATION
Therapy app cut A1c, drug intensification in T2D
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.
FROM ACC 2023
Prone positioning curbs need for intubation in nonintubated COVID-19 patients
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.
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.
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.
FROM SCCM 2023
COVID vs. flu: Which is deadlier?
a new study shows.
People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.
The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”
The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022.
Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%.
Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.
“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.
While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.
A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.
Four coauthors reported receiving grants and personal fees from various sources.
A version of this article first appeared on WebMD.com.
a new study shows.
People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.
The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”
The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022.
Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%.
Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.
“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.
While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.
A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.
Four coauthors reported receiving grants and personal fees from various sources.
A version of this article first appeared on WebMD.com.
a new study shows.
People who were hospitalized with Omicron COVID-19 infections were 54% more likely to die, compared with people who were hospitalized with the flu, Swiss researchers found.
The results of the study continue to debunk an earlier belief from the start of the pandemic that the flu was the more dangerous of the two respiratory viruses. The researchers noted that the deadliness of COVID-19, compared with flu, persisted “despite virus evolution and improved management strategies.”
The study was published in JAMA Network Open and included 5,212 patients in Switzerland hospitalized with COVID-19 or the flu. All the COVID patients were infected with the Omicron variant and hospitalized between Jan. 15, 2022, and March 15, 2022. Flu data included cases from January 2018 to March 15, 2022.
Overall, 7% of COVID-19 patients died, compared with 4.4% of flu patients. Researchers noted that the death rate for hospitalized COVID patients had declined since their previous study, which was conducted during the first COVID wave in the first half of 2020. At that time, the death rate of hospitalized COVID patients was 12.8%.
Since then, 98% of the Swiss population has been vaccinated. “Vaccination still plays a significant role regarding the main outcome,” the authors concluded, since a secondary analysis in this most recent study showed that unvaccinated COVID patients were twice as likely to die, compared with flu patients.
“Our results demonstrate that COVID-19 still cannot simply be compared with influenza,” they wrote.
While the death rate among COVID patients was significantly higher, there was no difference in the rate that COVID or flu patients were admitted to the ICU, which was around 8%.
A limitation of the study was that all the COVID cases did not have laboratory testing to confirm the Omicron variant. However, the study authors noted that Omicron accounted for at least 95% of cases during the time the patients were hospitalized. The authors were confident that their results were not biased by the potential for other variants being included in the data.
Four coauthors reported receiving grants and personal fees from various sources.
A version of this article first appeared on WebMD.com.
FROM JAMA NETWORK OPEN
Pfizer COVID vaccine effective in young children, study shows
A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.
A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”
The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.
The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.
When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.
Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.
Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.
A version of this article originally appeared on WebMD.com.
A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.
A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”
The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.
The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.
When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.
Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.
Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.
A version of this article originally appeared on WebMD.com.
A new study shows the Pfizer vaccine is safe and highly effective against COVID-19 in children as young as 6 months old.
A three-dose series of the Pfizer COVID-19 vaccine was 73% effective at preventing symptomatic COVID-19 in children aged 6 months to 4 years, the researchers found. They also found that an examination of reactions and safety results “did not suggest any concerns.”
The study, published in the New England Journal of Medicine, included 1,776 children aged 6 months to 2 years old, and 2,750 children aged 2-4 years. Children were randomly assigned to receive either the three-shot series of the Pfizer vaccine or placebo shots. Participants received the first dose of the vaccine by March 31, 2022, and lived in Brazil, Finland, Poland, Spain, or the United States.
The authors wrote that having safe and effective COVID vaccines for young children is important to protect them from hospitalization or death and because young children play a role in spreading highly transmissible variants of the virus. COVID hospitalizations for children under 5 years old peaked at a rate of 14.5 per 100,000 in January 2022, the authors wrote, noting that the Omicron virus variant appeared to affect young children more severely than the previous variant, Delta.
When the researchers evaluated vaccine effectiveness by age group, they found that it prevented symptomatic COVID in 75.8% of children aged 6 months to 2 years, and in 71.8% of children aged 2-4 years.
Less than 0.5% of participants reported severe reactions to the vaccine. The most common reactions reported were tenderness or pain. Reactions typically appeared within the first couple days following vaccine administration and resolved within 2 days. No cases of inflammation of the heart muscle or its lining were reported among participants.
Uptake of COVID vaccines for young children has been lower than other age groups in the United States. The Centers for Disease Control and Prevention says 10% of children younger than 5 have received at least one dose of a COVID-19 vaccine, and 5% have completed a primary vaccine series.
A version of this article originally appeared on WebMD.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
How to get started with prescribing and advising on CGM
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.
Continuous glucose monitoring (CGM) is gaining ground with both patients and providers because of an array of driving forces, including broadening eligibility, insulin price caps, public awareness, and an increasing number of educational initiatives for doctors.
While professional organizations aim to familiarize doctors with this relatively new technology, more patients are learning independently that finger sticks may be optional, leading them to request CGM from their provider, according to Neil Skolnik, MD.
“We in primary care are being shepherded into this space by our patients who have seen an advertisement or talked to a friend about the benefits of CGM, and then asked us to prescribe it,” said Dr. Skolnik, professor of family and community medicine at Sidney Kimmel Medical College, Philadelphia, and associate director of the family medicine residency program at Abington (Pa.) Hospital–Jefferson Health.
Systemic factors are also accelerating CGM uptake, he added, highlighting recent Medicare rule changes to expand eligibility, with insurance companies beginning to follow suit.
Warren A. Jones, MD, FAAFP, professor emeritus at the University of Mississippi, Jackson, and past president of the AAFP, said that insulin price regulations have also opened doors to CGM.
“When you had patients trying to determine whether they were going to buy food or pay for high-priced insulin, that was a big challenge,” Dr. Jones said in an interview. “But that barrier has recently been removed, so we’re at the dawn of a new era.”
Like any paradigm shift, however,
Overview of online resources and navigating coverage
The latest learning resource on CGM for physicians comes from the American Academy of Family Physicians in the form of a new online educational hub with a 2-credit, ACCME-accredited course. It offers comprehensive guidance for employing CGM in daily practice. Topics include both medical and practical considerations, from interpretation of curves and glucose goal-setting to choosing a device and navigating coverage.
The AAFP’s new offering joins a growing number of similar educational efforts launched over the past few years by the Association of Diabetes Care & Education Specialists, the American Pharmacists Association, the American Diabetes Association, and the American Association of Clinical Endocrinologists.
Checking for coverage is a key first step when considering CGM for a particular patient, Dr. Jones said, noting that CGM, like any new form of care, presents unique challenges with coding and claims that must be overcome to get reimbursed.
“No margin, no mission,” Dr. Jones said. “If you are not able to pay your bills, you can’t be available for your patients. Our goal at the AAFP is to make sure that physicians get this knowledge [about reimbursement].”
To this end, the AAFP’s new online educational hub and the guide provided by APhA present CGM eligibility criteria for various patient groups, including those with Medicare, Medicaid, private insurance, and without coverage.
Medicare criteria include a diagnosis of diabetes, treatment with three or more daily administrations of insulin or continuous infusion via a pump, frequent adjustment to insulin treatment based on glucose readings, and presentation for diabetes in the past 6 months.
Once these requirements are clearly documented in the patient’s record, providers need to write the script, complete a certificate of medical necessity, and choose a supplier. Medicare covers CGM as a durable medical equipment benefit instead of a pharmacy benefit, according to the AAFP and APhA.
Exact coverage criteria and reimbursement processes for non-Medicare patients follow similar paths, although details vary by state and insurer, so personalized investigation is required.
When exploring coverage, the AAFP recommends paying attention to information needed for prior authorization, the patient’s diabetes type and age, and other medical requirements, such as minimum number of daily finger sticks or insulin doses per day.
Looking ahead, Dr. Jones predicted that authorization obstacles stemming from short-term cost concerns are going to fade as long-term savings are uncovered.
“I think pharmacy benefit managers and payers are going to recognize that we have better patient compliance, and that continuous glucose monitoring is going to bring the cost of care down and decrease the rate of hospitalizations,” Dr. Jones said. “So I think they’re going to be willing to pay clinicians to engage in this more readily over time.”
Patients who fail to qualify for personal CGM can still benefit from professional CGM, in which they borrow necessary equipment on a short-term basis. This avenue typically requires minimal or no insurance authorization. In addition, providers have the “opportunity to cover/exceed expenses by enhancing revenue with separately billable procedures, which can be billed in addition to [evaluation and management] if done on same day,” according to the AAFP guide, which goes on to provide appropriate codes.
Learning CGM through first-hand experience
Getting started with CGM can be intimidating for providers, Dr. Skolnik said, although he offered some reassurance, suggesting that the learning process may be more forgiving than prescribing a new drug for the first time.
“I think the best way to figure out CGM is to prescribe it to a couple of patients and learn with them,” Dr. Skolnik said. “You can’t do that with medicines. With medicines, you need to know what you’re doing before you choose who to give a medicine to.”
Instead of “reading everything under the sun” about CGM, he recommends starting with several of the ADA’s resources focusing on time in range, including an article, webinar, and podcast.
After that, physicians can learn on the job. A beginner’s mindset to CGM is well received by patients, he said, especially if you share your natural curiosity with them.
“Share your patients’ wonder at what they see,” Dr. Skolnik said. “They’ll open the app and you’ll look at their time and range and together you’ll go, ‘Wow, isn’t that something? I wonder why?’ ”
With this approach, providers and patients can join forces to explore trends and troubleshoot anomalous readings.
“Together you’ll go: ‘Hmm, I wonder why on Thursday, that graph is looking so far off from the other days? Wow. And then the patient remembers: they ate out on Thursday. They had a big pasta meal, perhaps. Everyone’s different in how they respond to different carbs. And you’ll both have this epiphany together about: ‘Wow, what I do matters.’ And I think that’s actually the best way to jump in.”
According to the AAFP, ADCES, and APhA resources, providers should first address time below range, as hypoglycemia can be imminently dangerous.
Next, providers should consider time in range, average glucose, and glucose management indicator, the latter of which acts as a surrogate for HbA1c. The first couple weeks of monitoring should be viewed as an information gathering phase, after which specific targets can be addressed through behavioral modifications and insulin adjustments, the AAFP advises.
The ADA guide highlights CGM usage, glucose variability, time in range, time above range, and average glucose as key metrics to monitor and offers corresponding actions when targets are unmet.
Encouraging patients to start CGM
Like providers, patients may also be intimidated by CGM, Dr. Jones said, typically because they don’t know how it works, or it seems complicated. Fortunately, he said, these fears are easily overcome when patients learn that they don’t need to stick themselves, record any of their readings, or really do anything at all for the first few weeks.
“You don’t even worry about it,” Dr. Jones tells his patients, who typically feel “more in control and engaged in their own care” after experiencing CGM for themselves.
Dr. Jones speaks from both professional and personal experience. A member of his family recently started CGM after being discharged from the hospital, and the benefits have been significant for everyone involved.
“I see how effectively we can control [my family member’s] blood pressure and insulin requirements, as opposed to several months ago when we didn’t have it,” Dr. Jones said. “So I’m giving it to you from two perspectives: one, of the clinician who knows, intellectually, what should go on, and two, experientially, from a family trying to take care of someone they love.”
Dr. Skolnik disclosed relationships with AstraZeneca, Teva, Lilly, Boehringer Ingelheim, Sanofi, GSK, Bayer, Genentech, Abbott, Idorsia, Merck, Novartis, Heartland, and Novo Nordisk. Dr Jones disclosed no relevant conflicts of interest.
COVID infection provides immunity equal to vaccination: Study
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
People who’ve been infected with COVID reduced their chances of hospitalization and death by 88% over 10 months compared to somebody who hasn’t been infected, according to the study, published in The Lancet.
The natural immunity provided by infection was “at least as high, if not higher” than the immunity provided by two doses of Moderna or Pfizer mRNA vaccines against the ancestral, Alpha, Delta, and Omicron BA.1 variants, the researchers reported.
But protection against the BA.1 subvariant of Omicron was not as high – 36% at 10 months after infection, wrote the research team from the Institute for Health Metrics and Evaluation at the University of Washington.
They examined 65 studies from 19 countries through Sept. 31, 2022. They did not study data about infection from Omicron XBB and its sub-lineages. People who had immunity from both infection and vaccination, known as hybrid immunity, were not studied.
The findings don’t mean people should skip the vaccines and get COVID on purpose, one of the researchers told NBC News.
“The problem of saying ‘I’m gonna get infected to get immunity’ is you might be one of those people that end up in the hospital or die,” said Christopher Murray, MD, DPhil, director of the IHME. “Why would you take the risk when you can get immunity through vaccination quite safely?”
The findings could help people figure out the most effective time to get vaccinated or boosted and guide officials in setting policies on workplace vaccine mandates and rules for high-occupancy indoor settings, the researchers concluded.
This was the largest meta-analysis of immunity following infection to date, NBC News reports.
A version of this article originally appeared on WebMD.com.
FROM THE LANCET
Untreated COVID often involves relapse, clarifying antiviral rebound discussion
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
These findings offer a natural history of COVID-19 that will inform discussions and research concerning antiviral therapy, lead author Jonathan Z. Li, MD, associate professor of infectious disease at Brigham and Women’s Hospital and Harvard Medical School, both in Boston, and colleagues reported in Annals of Internal Medicine.
“There are increasing reports that high-risk patients are avoiding nirmatrelvir-ritonavir due to concerns about post-Paxlovid rebound, but there remains a gap in our knowledge of the frequency of symptom and viral relapse during untreated natural infection,” Dr. Li said in a written comment.
To address this gap, Dr. Li and colleagues analyzed data from 563 participants from the placebo group of the Adaptive Platform Treatment Trial for Outpatients with COVID-19 (ACTIV-2/A5401).
From days 0-28, patients recorded severity of 13 symptoms, with scores ranging from absent to severe (absent = 0, mild = 1, moderate = 2, severe = 3). RNA testing was performed on samples from nasal swabs on days 0–14, 21, and 28.
“The symptom rebound definition was determined by consensus of the study team, which comprises more than 10 infectious disease, pulmonary, and critical care physicians, as likely representing a clinically meaningful change in symptoms,” Dr. Li said.
Symptom scores needed to increase by at least 4 points to reach the threshold. For instance, a patient would qualify for relapse if they had worsening of four symptoms from mild to moderate, emergence of two new moderate symptoms, or emergence of one new moderate and two new mild symptoms.
The threshold for viral relapse was defined by an increase of at least 0.5 log10 RNA copies/mL from one nasal swab to the next, while high-level viral relapse was defined by an increase of at least 5.0 log10 RNA copies/mL. The former threshold was chosen based on previous analysis of viral rebound after nirmatrelvir treatment in the EPIC-HR phase 3 trial, whereas the high-level relapse point was based on Dr. Li and colleagues’ previous work linking this cutoff with the presence of infectious virus.
Their present analysis revealed that 26% of patients had symptom relapse at a median of 11 days after first symptom onset. Viral relapse occurred in 31% of patients, while high-level viral relapse occurred in 13% of participants. In about 9 out 10 cases, these relapses were detected at only one time point, suggesting they were transient. Of note, symptom relapse and high-level viral relapse occurred simultaneously in only 3% of patients.
This lack of correlation was “surprising” and “highlights that recovery from any infection is not always a linear process,” Dr. Li said.
This finding also suggests that untreated patients with recurring symptoms probably pose a low risk of contagion, according to David Wohl, MD, coauthor of the paper and professor of medicine in the division of infectious diseases at the University of North Carolina at Chapel Hill.
Paxlovid may not be to blame for COVID-19 rebound
“These results provide important context for the reports of Paxlovid rebound and show that baseline rates of symptom and viral relapse should be accounted for when studying the risk of rebound after antiviral therapy,” Dr. Li said.
Dr. Wohl suggested that these data can also play a role in conversations with patients who experience rebound after taking antiviral therapy.
“Many who have a return of their symptoms after taking Paxlovid blame the drug, and that may be justified, but this study suggests it happens in untreated people too,” Dr. Wohl said in a written comment.
Longer antiviral therapy deserves investigation
This is a “very important study” because it offers a baseline for comparing the natural history of COVID-19 with clinical course after antiviral therapy, said Timothy Henrich, MD, associate professor in the division of experimental medicine at University of California, San Francisco.
“Unlike this natural history, where it’s kind of sputtering up and down as it goes down, [after antiviral therapy,] it goes away for several days, and then it comes back up; and when it comes up, people have symptoms again,” Dr. Henrich said in an interview.
This suggests that each type of rebound is a unique phenomenon and, from a clinical perspective, that antiviral therapy may need to be extended.
“We treat for too short a period of time,” Dr. Henrich said. “We’re able to suppress [SARS-CoV-2] to the point where we’re not detecting it in the nasal pharynx, but it’s clearly still there. And it’s clearly still in a place that can replicate without the drug.”
That said, treating for longer may not be a sure-fire solution, especially if antiviral therapy is started early in the clinical course, as this could delay SARS-CoV-2-specific immune responses that are necessary for resolution, Dr. Henrich added,
“We need further study of longer-term therapies,” he said.
An array of research questions need to be addressed, according to Aditya Shah, MBBS, an infectious disease specialist at Mayo Clinic, Rochester, Minn. In a written comment, he probed the significance of rebound in various clinical scenarios.
“What [type of] rebound matters and what doesn’t?” Dr. Shah asked. “Does symptom rebound matter? How many untreated and treated ‘symptom rebounders’ need additional treatment or health care? If rebound does not really matter, but if Paxlovid helps in certain unvaccinated and high-risk patients, then does rebound matter? Future research should also focus on Paxlovid utility in vaccinated but high-risk patients. Is it as beneficial in them as it is in unvaccinated high-risk patients?”
While potentially regimen-altering questions like these remain unanswered, Dr. Henrich advised providers to keep patients focused on what we do know about the benefits of antiviral therapy given the current 5-day course, which is that it reduces the risk of severe disease and hospitalization.
The investigators disclosed relationships with Merck, Gilead, ViiV, and others. Dr. Henrich disclosed grant support from Merck and a consulting role with Roche. Dr. Shah disclosed no conflicts of interest.
FROM ANNALS OF INTERNAL MEDICINE
Diabetes drug tied to lower dementia risk
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY