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Pancreatic cancer incidence increases among young women in U.S.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
Between 2001 and 2018, there was a greater than 200% difference in the incidence trend between men and women for ages 15-34, wrote Yazan Abboud, MD, a postdoctoral research fellow in the pancreaticobiliary department of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai Medical Center, Los Angeles, and colleagues.
“The exact cause of the trend among younger women is unclear and may be driven by sex-based disproportional exposure or response to known or yet-to-be-explored risk factors,” they wrote. “Future efforts should aim to elucidate the causes of such a trend with the goal to formulate possible preventive measures.”
Although previous studies have found increasing pancreatic cancer incidence rates, especially in younger women, the data haven’t been externally validated outside of the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data, they wrote. In addition, there are limited data about the contributing factors, such as race, histopathological subtype, tumor location, and stage at diagnosis.
Using SEER-excluded data from the Centers for Disease Control and Prevention’s National Program of Cancer Registries (NPCR), Dr. Abboud and colleagues conducted a population-based time-trend analysis of pancreatic cancer incidence rates from 2001 to 2018 in younger adults under age 55, including the role of demographics and tumor characteristics. They analyzed age-adjusted incidence rates (aIR), mortality rates, annual percentage change (APC), and average annual percentage change (AAPC) for ages 55 and older and ages 55 and younger. In addition, the research team evaluated the impact of incidence trends on sex-specific mortality trends in younger adults using the CDC’s National Center of Health Statistics database.
Between 2001 and 2018, 748,132 patients were diagnosed with pancreatic cancer. After excluding SEER data, 454,611 patients met the inclusion criteria. About 48.9% were women.
The overall aIR of pancreatic cancer during that time was 12.18 per 100,000 people. Women had a significantly lower aIR, at 10.69 per 100,000, compared with men at 13.95 per 100,000.
In general, pancreatic cancer aIR significantly increased during that time (AAPC = 1.17%). Sex-specific trends increased among both women (AAPC = 1.27%) and men (AAPC = 1.14%), though they showed no significant difference and were parallel.
In ages 55 and older, 401,419 patients (49.7% women) were diagnosed with pancreatic cancer. The aIR significantly increased during the study period (AAPC = 1.11%), with sex-specific aIR increasing in both women (AAPC = 1.11%) and men (AAPC = 1.17%), without a significant difference.
However, a difference appeared in the 53,051 patients (42.9% women) who were ages 55 and younger. The aIR relatively increased (AAPC = 1.29%), with faster jumps in women (AAPC = 2.36%), compared with men (AAPC = .62%). There was an absolute significant difference of 1.74%.
The trends continued in breakdowns by age. For 50,599 patients (42.2% women) between ages 35 and 54, the aIR relatively increased (AAPC = 1.10%). Sex-specific aIR increased among women (AAPC = 2.09%) but remained stable among men (AAPC = 0.54%), with an absolute significant difference of 1.55%.
In the youngest cohort of 2,452 patients (57.3% women) between ages 15 and 34, aIR relatively increased (AAPC = 4.93). Sex-specific aIR also increased in both women (AAPC = 6.45%) and men (AAPC = 2.97%), with an absolute significant difference of 3.48%.
By race, although White women under age 55 experienced increasing aIR at a greater rate than men (AAPC difference = 1.59%), an even more dramatic increase was seen in Black women, as compared to counterpart men (AAPC difference = 2.23%). Sex-specific trends in people of other races were parallel.
Based on tumor characteristics in ages 55 and younger, the pancreatic ductal adenocarcinoma histopathological subtype had an AAPC difference of 0.89%, and a tumor location in the head-of-pancreas had an AAPC difference of 1.64%.
When evaluating tumors based on stage-at-diagnosis, the AAPC difference was nonsignificant in all subgroups. However, sex-specific trends differed in tumors diagnosed at localized stages, suggesting that aIR in women may be increasing at a greater rate than in men (AAPC difference = 1.64%).
Among 64,239 patients (39.3% women) who died from pancreatic cancer under age 55, the mortality rates were unchanged in women (AAPC = –0.09%) but declined in men (AAPC = –0.64%), with an absolute significant AAPC difference of 0.54%.
“Pancreatic cancer has a very poor overall survival, accounting for 7% of cancer-related deaths. The incidence of cancers, in general, is expected to rise as life expectancy increases in the United States,” said Danny Issa, MD, a gastroenterologist at the University of California, Los Angeles, who wasn’t involved with this study.
“Recently, noncomparative studies showed a possible increase in the incidence of pancreatic cancer in younger White women and in older White men and women. These reports had limitations,” he said. “The findings of this study are monumental as they confirmed that age-adjusted incidence rates have been increasing at a higher rate in younger women compared to younger men.”
In addition, Dr. Issa said, the significant increases among Black women for adenocarcinoma and for cancers located in the head of the pancreas are notable and should be studied further.
“Over the past few decades, research studies have helped improve cancer treatment by uncovering risk factors and identifying the most affected (or protected) population,” he said. “Therefore, epidemiologic studies are crucial, especially for hard-to-treat cancers such as pancreatic cancer.”
The study was supported in part by a philanthropic grant from The Widjaja Family Fund for Pancreatic Cancer Research. The authors disclosed no conflicts of interest. Dr. Issa reported no relevant disclosures.
FROM GASTROENTEROLOGY
Scientific advances and dietary measures to slow down aging
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
These findings are closer than ever to being applied in older adults. Currently, diet is the most accessible form of intervention, but it is appropriate to clarify current myths and realities.
An article published in Cell in 2013 summarized for the first time the molecular indicators of aging in mammals. The article had a great impact and served as a knowledge map about aging. Now the authors have updated and extended this knowledge in the same journal.
A barometer of interest in the topic is that approximately 300,000 articles on aging have been published since 2013, which is as many as were published during the previous century. In addition, almost 80 experiments have been conducted with mammals, including humans, that confirm that interventions in the aging process can prevent, delay, and even avoid age-related diseases such as cancer.
María A. Blasco, MD, scientific director of the National Cancer Research Center, an international leader in telomere research and coauthor of the study, noted on the institution’s website, “The spectacular advances in recent years to increase the longevity of model organisms, including in mammals, indicate that it will be important to develop rational strategies to intervene in human aging.”
Eighty experimental interventions
The new article verifies the conclusions of the analysis carried out a decade ago. “Now there is much more investment, and we are closer to applying basic knowledge to new ways of treating diseases,” said Dr. Blasco. The researchers identified nine indicators of aging – molecular signatures that mark the progress of the process and on which it was possible to act to prolong life.
They also point to four primary causes of aging: genomic instability, shortening of telomeres, epigenetic alterations, and imbalance between protein synthesis and degradation. These are strongly interconnected processes. Aging results from their joint action, which is why there are multiple ways to act on the physiologic process of aging. The new study includes a table with almost 80 recent experimental interventions with mammals (mostly mice) that suggest that it is possible to prolong life or treat age-associated diseases. Some of those studies concern humans; others investigate how to delay aging through diet. “Acting on the diet is one of the most accessible ways to intervene in human aging,” according to the researchers.
Nutrient sensors
Dietary interventions are related to a key indicator of aging: the dysregulation of the nutrient sensing mechanism. This mechanism is the sophisticated network of molecular signals that alert all mammals that food is available.
“Nutrient sensors are therapeutic targets for potential anti-longevity drugs, but health benefits and lifespan extension could also be achieved through dietary interventions. However, the results obtained in this line in our species are still unclear: Clinical trials based on dietary restriction in humans become complicated due to poor compliance, although they suggest positive effects on immunity and inflammation,” wrote the researchers.
Diet and disease
Javier Gómez Pavón, MD, head of geriatrics at Red Cross Hospital in Madrid and member of the leadership team of the Spanish Society of Geriatrics and Gerontology, told this news organization, “Currently, the evidence we have indicates that certain types of diet in population cohort studies are associated with a lower incidence and prevalence of certain diseases.”
Dr. Gómez mentioned contrasting examples. “The Mediterranean diet has been shown in different studies to be associated with a lower cardiovascular risk (stroke, ischemic heart disease, dyslipidemia) and a lower risk of cognitive impairment, especially due to its vascular component.”
Eating nuts (e.g., almonds, walnuts) is associated with a less dyslipidemia. A diet rich in fiber is also associated with less colonic digestive pathology, such as constipation and especially colon cancer. In addition, a diet low in fatty meats and rich in fruits and vegetables is associated with less prostate, breast, and colon disease. A diet with adequate protein intake is related to better muscle mass at all ages, and a diet rich in calcium products, such as nuts and dairy products, is linked to better bone mass and less osteoporosis and its consequences.
“At the moment, there is no study that links any type of diet with greater longevity, although in view of these data, it seems logical that a Mediterranean diet rich in fruits, vegetables, vegetables with proteins of animal origin, preferably fish or white meat, avoiding excess red meat and its calcium component in the form of nuts and dairy products would be associated with better disease-free aging,” said Dr. Gómez.
Aging indicators
The article expands the aging indicators from 9 to 12 (genomic instability, telomere wear, epigenetic alterations, loss of proteostasis, inactivated macroautophagy, dysregulation of nutrient sensing, mitochondrial dysfunction, cellular senescence, depletion of hematopoietic progenitor cells, alteration of intercellular communication, chronic inflammation, and imbalances in the microbiome), which are measurable processes that change with the aging of the organism and which, when manipulated experimentally, induce an acceleration or, on the contrary, an interruption, even a regression, of aging.
“Each of these indicators should be considered an entry point for future exploration of the aging process, as well as for the development of new antiaging drugs,” the researchers concluded.
A decade ago, it was recognized that telomere shortening was at the origin of age-related diseases, said Dr. Blasco. “It is now emphasized that the generation of mouse models with short telomeres has shown that telomeric wasting is at the origin of prevalent age-associated diseases, such as pulmonary and renal fibrosis.”
The recent study reviews new interventions to delay aging and age-related diseases that act on telomeres. “For example, the activation of telomerase through a gene therapy strategy has shown therapeutic effects in mouse models of pulmonary fibrosis and aplastic anemia,” Dr. Blasco added.
Food fact and fiction
Since diet is currently the most easily accessible element to slow down aging, Dr. Gómez refutes the most widespread myths that are circulating about food and longevity. First, regarding dairy products, it is said that yogurt is not useful for the elderly, since the elderly do not have adequate enzymes to digest yogurt and that it is only for children or young people who are growing. “It is not true. Dairy products are not important for their proteins but for their calcium and vitamin D content. [These are] fundamental elements at all ages, but especially in aging, where there is bone loss secondary to aging itself and an increased risk of osteoporosis and associated fractures. Especially in the elderly, the tragic hip fracture is associated with high morbidity and mortality.”
Another myth is that it is not good to eat fruit with meals. “Due to its rich content in antioxidants and vitamins, it is a fundamental food of the Mediterranean diet. Antioxidants of any type (nuts, vegetables, fruits, etc.) are undoubtedly the most important components against pathological aging (stroke, myocardial infarction, dementia, etc.). It may be true that they can be more easily digested if they are eaten outside of meals, but the important thing is that they be eaten whenever.”
Sugars and meat
“Regarding the ‘fact’ that the sugars in legumes and bread are harmful, it is not true. In addition to sugar, legumes contain fiber and other very important antioxidants, just like bread. The difference is the amount, as in all food. On the contrary, refined sugars, such as pastries, sugary drinks, etc., should be avoided, since they are directly related to cardiovascular disease and obesity,” added Dr. Gómez.
“As for the popular saying, ‘Do not even try meat,’ it is not sound, since red meat and fish, including oily fish, are rich in protein and vitamin B as well as iron and, therefore, are necessary.
“As always, it is the amount that should be limited, especially red meat, not so much oily fish. I would recommend reducing red meat and replacing it with white meat, since the former are rich in saturated fats that produce more cholesterol,” added Dr. Gómez.
Another phrase that circulates around is that wine is food. “Careful. Wine in small quantities, a glass at lunch and dinner, is beneficial due to its antioxidant power, but at more than these amounts, the negative power of alcohol predominates over its benefits,” concluded Dr. Gómez.
Dr. Gómez has disclosed no relevant financial relationships.
This article was translated from the Medscape Spanish edition. A version of this article appeared on Medscape.com.
FROM CELL
Myths about smoking, diet, alcohol, and cancer persist
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
FRANCE – Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.
This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
Is cancer hereditary?
The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.
“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.
Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
Misconceptions about smoking
About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.
Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.
“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.
This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
Overweight and obesity
Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.
“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
Breastfeeding and cancer
About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.
Artificial UV rays
Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.
Daily stress
Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.
Cigarettes and e-cigarettes
About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.
Alcohol consumption
Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”
This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.
Physician pleads guilty to 52 counts in opioid scheme
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
Jeffrey B. Sutton, DO, a neuromuscular medicine specialist, pled guilty on January 30 in federal court to 31 counts of illegally prescribing opioids and other controlled substances, 1 count of illegally distributing controlled substances, and 20 counts of health care fraud.
Prosecutors said Dr. Sutton admitted that he ignored warnings from prescription drug management organizations, insurers, and state authorities that he was prescribing excessively high dosages of opioids.
Dr. Sutton also admitted to ignoring patient requests to lower dosages and that he also ignored signs that patients were selling prescribed medications or otherwise engaging in illicit activity, including violations of a “pain management agreement” that he required them to sign.
The fraud counts pertained to Dr. Sutton billing Medicare, Medicaid, and other insurers for medically unnecessary visits that he required of patients so that he could prescribe inappropriate or unnecessary opioids.
In the charging document shared with this news organization, prosecutors said Dr. Sutton had sex with at least three patients, including during office visits and outside of the office. Occasionally, the physician would give opioids or other controlled substances – often benzodiazepines – to these patients, without a prescription or valid medical need.
Dr. Sutton escalated the dosage for one of those patients, even as the subjective pain score did not improve and when the patient’s urine tests showed the presence of THC and buprenorphine, but not any of the prescribed medications.
Another patient came to Dr. Sutton in 2007 with a warning that she had a history of “narcotic-seeking” behavior and diagnoses of depression, anxiety, paranoid schizophrenia, and obsessive-compulsive disorder.
The patient was hospitalized in 2018 for complications from benzodiazepine use (prescribed by Dr. Sutton). She weighed 80 pounds at the time. Dr. Sutton continued to prescribe benzodiazepines and extreme doses of opioids – in excess of 2,000 morphine equivalent dose – “despite recognizing and documenting repeated instances of noncompliance with treatment for psychiatric conditions, and despite the known contraindications of long-term opioid use for patients with these mental illnesses,” according to the charging document.
Dr. Sutton continued to prescribe opioids despite two hospitalizations for overdoses, more than 20 failed urine drug screens that showed presence of illicit drugs such as cocaine, and documented excessive use of alprazolam (Xanax) and methadone.
The physician surrendered his Drug Enforcement Administration Certificate of Registration of Controlled Substances Privileges in February 2022 “as an indication of your good faith in desiring to remedy any incorrect or unlawful practices on your part,” according to a letter to Dr. Sutton from the State Medical Board of Ohio. In that September 2022 letter, the Board notified Dr. Sutton of its intention to possibly suspend or revoke his license.
Dr. Sutton did not request a hearing, and the Board permanently revoked his medical license on January 16.
The court will sentence Dr. Sutton on May 23, according to a report by WFMJ.
A version of this article originally appeared on Medscape.com.
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
Concussion burden tied to later hypertension in football players
a new study suggests.
Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.
“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.
“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”
The study was published online in Circulation.
Link to cognitive decline?
Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.
Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.
Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.
Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.
A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.
After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.
Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.
“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.
While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.
“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.
Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
Close monitoring
Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.
“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.
Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.
Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling.
The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”
He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”
The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.
A version of this article originally appeared on Medscape.com.
a new study suggests.
Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.
“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.
“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”
The study was published online in Circulation.
Link to cognitive decline?
Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.
Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.
Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.
Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.
A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.
After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.
Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.
“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.
While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.
“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.
Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
Close monitoring
Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.
“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.
Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.
Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling.
The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”
He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”
The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.
A version of this article originally appeared on Medscape.com.
a new study suggests.
Among more than 4,000 participants, 37% had hypertension at a median of 24 years post career and reported a median concussion symptom score (CSS) of 23 on a scale of 0 to 130.
“We have long seen an incompletely explained link between football participation and later-life cardiovascular disease,” Aaron L. Baggish, MD, of Massachusetts Hospital and Harvard Medical School, Boston, told this news organization.
“This study tested [whether] concussion burden during years of active play would be a determinant of later-life hypertension, the most common cause of cardiovascular disease, and indeed found this relationship to be a strong one.”
The study was published online in Circulation.
Link to cognitive decline?
Dr. Baggish and colleagues recruited former professional American-style football (ASF) players to participate in a survey administered by the Football Players Health Study at Harvard University.
Concussion burden was quantified with respect to the occurrence and severity of common concussion symptoms – e.g., headaches, nausea, dizziness, confusion, loss of consciousness (LOC), disorientation, and feeling unsteady on one’s feet – over years of active participation.
Prevalent hypertension was determined either by the participants’ previously receiving from a clinician a recommendation for medication for “high blood pressure” or by the participants’ taking such medication at the time of survey completion. Diabetes status was determined by the participants’ receiving a prior recommendation for or prescription for “diabetes or high blood sugar” medication.
Of 15,070 invited to participate in the study, 4,168 did so. The mean age of the participants was 51.8 years; 39.4% were Black; the mean body mass index was 31.3; and 33.9% were linemen. Participants played for a mean of 6.9 seasons and were surveyed at a median 24.1 years post ASF career completion. The median CSS was 23.
A total of 1,542 participants (37.3%) had hypertension, and 8.8% had diabetes.
After adjustment for established hypertension risk factors, including smoking, race, diabetes, age, and BMI, there was a graded association between CSS category and odds of later-life hypertension and between high CSS exposure and prevalent hypertension.
Results persisted when LOC, a single highly specific severe concussion symptom, was used in isolation as a surrogate for CSS, the investigators noted.
“These results suggest that repetitive early-life brain injury may have later-life implications for cardiovascular health,” they wrote. They also noted that hypertension has been shown to independently increase the risk of cognitive decline.
While premature cognitive decline among ASF players is generally attributed to chronic traumatic encephalopathy, “data from the current study raise the possibility that some element of cognitive decline among former ASF players may be attributable to hypertension,” which is potentially treatable.
“Future studies clarifying associations and causal pathways between brain injury, hypertension, and brain health are warranted,” they concluded.
Dr. Baggish added, “We hope that clinicians will now understand that head injury is an independent risk factor for high blood pressure and will screen vulnerable populations accordingly, as this may lead to better recognition of previously underdiagnosed hypertension with subsequent opportunities for intervention.”
Close monitoring
Commenting on the study, Jonathan Kim, MD, chair-elect of the American College of Cardiology’s Sports–Cardiology Section and chief of sports cardiology at Emory University in Atlanta, said, “They clearly show an independent association, which is not causality but is a new finding that requires more research. To me, it really emphasizes that cardiovascular risk is the most important health consequence that we should be worried about in retired NFL [National Football League] players.
“There are multifactorial reasons – not just repetitive head trauma – why this athletic population is at risk for the development of high blood pressure, even among college players,” he said.
Dr. Kim’s team has shown in studies conducted in collaboration with Dr. Baggish and others that collegiate football players who gain weight and develop increased systolic blood pressure are at risk of developing a “pathologic” cardiovascular phenotype.
Other research from this group showed links between nonsteroidal anti-inflammatory drug use among high school and collegiate ASF players and increased cardiovascular risk, as well as ASF-associated hypertension and ventricular-arterial coupling.
The suggestion that late-life hypertension could play a role in premature cognitive decline among ASF players “warrants further study,” Dr. Kim said, “because we do know that hypertension in the general population can be associated with cognitive decline. So that’s an important future direction.”
He concluded: “It’s a matter of focusing on cardiac prevention.” After their careers, players should be counseled on the importance of losing weight and adopting heart-healthy habits. In addition to some of the traditional concerns that might lead to closer follow-up of these patients, “having a lot of concussions in the history could potentially be another risk factor that should warrant close monitoring of blood pressure and, of course, treatment if necessary.”
The study was supported by Harvard Catalyst/the Harvard Clinical and Translational Science Center and the NFL Players Association. Dr. Baggish and several coauthors have received funding from the NFL Players Association.
A version of this article originally appeared on Medscape.com.
FROM CIRCULATION
Advanced imaging technology could help predict lung cancer progression after surgery
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, according to new data.
The technology, known as highly multiplexed imaging mass cytometry (IMC), can provide cellular-level detail of the tumor immune microenvironment, which may allow clinicians to identify patients who need additional treatment, as well as those who don’t.
“It is well known that the frequency of certain cell populations within the tumor microenvironment correlates with clinical outcomes. These observations help us understand the biology underlying cancer progression,” senior author Logan Walsh, PhD, assistant professor of human genetics and the Rosalind Goodman Chair in Lung Cancer Research at McGill University’s Rosalind and Morris Goodman Cancer Institute, Montreal, said in an interview.
“We wanted to test whether using completely unbiased AI could find and use the spatial topography of the tumor microenvironment from IMC data to predict clinical outcomes,” he said. “It turns out the answer is yes! AI can predict clinical outcomes when combined with IMC with extremely high accuracy from a single 1-mm2 tumor core.”
The study was published on in Nature.
The immune landscape
Lung cancer is the leading cause of cancer-related death in Canada, surpassing breast, colon, and prostate cancer deaths combined, the study authors write.
Lung adenocarcinoma, a non–small cell lung cancer, is the most common subtype and is characterized by distinct cellular and molecular features. The tumor immune microenvironment influences disease progression and therapy response, the authors write. Understanding the spatial landscape of the microenvironment could provide insight into disease progression, therapeutic vulnerabilities, and biomarkers of response to existing treatments.
In a collaborative study, Dr. Walsh and colleagues from McGill University and Université Laval profiled the cellular composition and spatial organization of the tumor immune microenvironment in tumors from 416 patients with lung adenocarcinoma across five histologic patterns. They used IMC to assess at samples from the universities’ biobanks that patients had provided for research purposes.
The research team detected more than 1.6 million cells, which allowed spatial analysis of immune lineages and activation states with distinct clinical correlates, including survival. They used a supervised lineage assignment approach to classify 14 distinct immune cell populations, along with tumor cells and endothelial cells.
High-grade solid tumors had the greatest immune infiltrate (44.6%), compared with micropapillary (37%), acinar (39.7%), papillary (32.8%), and lepidic architectures (32.7%). Macrophages were the most frequent cell population in the tumor immune microenvironment, representing 12.3% of total cells and 34.1% of immune cells.
The prevalence of CD163+ macrophages was strongly correlated with FOXP3+ immunoregulatory T cells in the solid pattern. This relationship was less pronounced in low-grade lepidic and papillary architectures. This finding could suggest an interplay between macrophage and T-cell populations in the tumor immune microenvironment across lung adenocarcinoma patterns.
Using a deep neural network model, the researchers also analyzed the relationship between immune populations and clinical or pathologic variables by examining the frequency of individual cell types as a percentage of total cells in each image. Each image was cross-referenced with clinical data from patients, including sex, age, body mass index, smoking status, stage, progression, survival, and histologic subtype.
Overall, the researchers found that various clinical outcomes, including cancer progression, could be predicted with high accuracy using a single 1-mm2 tumor core. For instance, they could predict progression in stage IA and IB resected lung cancer with 95.9% accuracy.
Additional applications
“We were not surprised that AI was able to predict clinical outcomes, but we were surprised that it was able to do so with such high accuracy and precision,” said Dr. Walsh. “We were also surprised to learn that our predictions were equally accurate using only six-plex data, compared with 35-plex. This hinted to us that we could potentially scale down the number of markers to a practical number that would be amenable to technologies available in routine pathology labs.”
Dr. Walsh and colleagues are now validating the predictive tool using a lower-plex technology. In addition, they are investigating the immune landscapes of primary and metastatic brain tumors.
“This study is important, as it helps us to understand and appreciate the biological and mechanistic factors that may influence treatment outcomes. Our standard clinical predictors for predicting risk of recurrence and probability of response to therapy are not optimal,” Yee Ung, MD, an associate professor of radiation oncology at Sunnybrook Health Sciences Centre, Toronto, said in an interview.
Dr. Ung, who wasn’t involved with this study, has researched noninvasive hypoxia imaging and targeting in lung cancer. Ideally, he said, future studies should incorporate the use of noninvasive imaging predictive factors, in addition to the tumor immune microenvironment and clinical factors, to predict outcomes and provide personalized treatment.
“As we begin to investigate and understand more about cancer biology down to the cellular and molecular level, we need to strategically use AI methodologies in the processing and analysis of data,” he said.
The study was supported by the McGill Interdisciplinary Initiative in Infection and Immunity, the Brain Tumour Funders’ Collaborative, the Canadian Institutes of Health Research, and the Canadian Foundation for Innovation. Dr. Walsh and Dr. Ung have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NATURE
VA Plans to Waive Health Care Copayments for American Indian Veterans
New VA rule proposes to eliminate many copays for Native American veteran.
The US Department of Veterans Affairs (VA) has proposed a new rule that would waive medical copayments incurred on or after January 5, 2022, for eligible American Indian and Alaska Native (AI/AN) veterans.
The policy is intended to encourage veterans to seek regular primary care treatment, the VA says. “It’s no mystery to a lot of people that health care is sometimes hard to come by in many Native American communities,” Travis Trueblood, director of the VA Office of Tribal Health, told reporters in January. “So, this effort by VA will enhance getting people into the facilities, helping them feel welcome and getting them to use those benefits that they've earned.”
Copayments for more than 3 visits to community-based urgent care in any calendar year would still be required. Follow-up care provided by a VA-authorized primary care provider would be exempt from copays. Members of federally recognized tribes are already exempt from copays at Indian Health Service clinics.
Eligibility may be based in part on documentation issued by AI/AN tribal governments to show tribal membership. The VA has proposed the documentation requirement “as this recognizes tribal sovereignty and promotes the Nation-to-Nation relationship that exists between the United States and tribal governments.” The requirement, the notice says, is consistent with the preferences of tribal leaders.
The regulation implements a requirement in the Johnny Isakson and David P. Roe, MD, Veterans Health Care and Benefits Improvement Act of 2020, which prohibited the VA from collecting copayments from AI/AN veterans for hospital care or medical services. Senator Jon Tester (D-MT), chair of the Senate Veterans’ Affairs Committee, and Senator Jerry Moran (R-KS) introduced legislation in 2020 to enact the new policy in January 2022 , which is why the rule is retroactive.
Congress passed the measure as part of a package of veterans’ legislation at the end of 2020, and then-President Donald Trump signed it into law in January 2021. Trueblood said the nature of the federal rulemaking process makes it hard to say exactly when the change will take effect, but that no veteran will be turned away from VA care for not making a copayment, even before the rule is finalized. The VA plans to reimburse eligible veterans who received care in the past year for copayment costs.
“I’m encouraged to see VA answering my call to implement the law and remove burdensome copayments for Native veterans accessing their earned health care,” said Tester in a press release. “The fact is Native veterans have bravely answered the call to duty for generations. And I’ll continue to hold VA accountable in delivering these veterans their long-overdue support.”
New VA rule proposes to eliminate many copays for Native American veteran.
The US Department of Veterans Affairs (VA) has proposed a new rule that would waive medical copayments incurred on or after January 5, 2022, for eligible American Indian and Alaska Native (AI/AN) veterans.
The policy is intended to encourage veterans to seek regular primary care treatment, the VA says. “It’s no mystery to a lot of people that health care is sometimes hard to come by in many Native American communities,” Travis Trueblood, director of the VA Office of Tribal Health, told reporters in January. “So, this effort by VA will enhance getting people into the facilities, helping them feel welcome and getting them to use those benefits that they've earned.”
Copayments for more than 3 visits to community-based urgent care in any calendar year would still be required. Follow-up care provided by a VA-authorized primary care provider would be exempt from copays. Members of federally recognized tribes are already exempt from copays at Indian Health Service clinics.
Eligibility may be based in part on documentation issued by AI/AN tribal governments to show tribal membership. The VA has proposed the documentation requirement “as this recognizes tribal sovereignty and promotes the Nation-to-Nation relationship that exists between the United States and tribal governments.” The requirement, the notice says, is consistent with the preferences of tribal leaders.
The regulation implements a requirement in the Johnny Isakson and David P. Roe, MD, Veterans Health Care and Benefits Improvement Act of 2020, which prohibited the VA from collecting copayments from AI/AN veterans for hospital care or medical services. Senator Jon Tester (D-MT), chair of the Senate Veterans’ Affairs Committee, and Senator Jerry Moran (R-KS) introduced legislation in 2020 to enact the new policy in January 2022 , which is why the rule is retroactive.
Congress passed the measure as part of a package of veterans’ legislation at the end of 2020, and then-President Donald Trump signed it into law in January 2021. Trueblood said the nature of the federal rulemaking process makes it hard to say exactly when the change will take effect, but that no veteran will be turned away from VA care for not making a copayment, even before the rule is finalized. The VA plans to reimburse eligible veterans who received care in the past year for copayment costs.
“I’m encouraged to see VA answering my call to implement the law and remove burdensome copayments for Native veterans accessing their earned health care,” said Tester in a press release. “The fact is Native veterans have bravely answered the call to duty for generations. And I’ll continue to hold VA accountable in delivering these veterans their long-overdue support.”
New VA rule proposes to eliminate many copays for Native American veteran.
The US Department of Veterans Affairs (VA) has proposed a new rule that would waive medical copayments incurred on or after January 5, 2022, for eligible American Indian and Alaska Native (AI/AN) veterans.
The policy is intended to encourage veterans to seek regular primary care treatment, the VA says. “It’s no mystery to a lot of people that health care is sometimes hard to come by in many Native American communities,” Travis Trueblood, director of the VA Office of Tribal Health, told reporters in January. “So, this effort by VA will enhance getting people into the facilities, helping them feel welcome and getting them to use those benefits that they've earned.”
Copayments for more than 3 visits to community-based urgent care in any calendar year would still be required. Follow-up care provided by a VA-authorized primary care provider would be exempt from copays. Members of federally recognized tribes are already exempt from copays at Indian Health Service clinics.
Eligibility may be based in part on documentation issued by AI/AN tribal governments to show tribal membership. The VA has proposed the documentation requirement “as this recognizes tribal sovereignty and promotes the Nation-to-Nation relationship that exists between the United States and tribal governments.” The requirement, the notice says, is consistent with the preferences of tribal leaders.
The regulation implements a requirement in the Johnny Isakson and David P. Roe, MD, Veterans Health Care and Benefits Improvement Act of 2020, which prohibited the VA from collecting copayments from AI/AN veterans for hospital care or medical services. Senator Jon Tester (D-MT), chair of the Senate Veterans’ Affairs Committee, and Senator Jerry Moran (R-KS) introduced legislation in 2020 to enact the new policy in January 2022 , which is why the rule is retroactive.
Congress passed the measure as part of a package of veterans’ legislation at the end of 2020, and then-President Donald Trump signed it into law in January 2021. Trueblood said the nature of the federal rulemaking process makes it hard to say exactly when the change will take effect, but that no veteran will be turned away from VA care for not making a copayment, even before the rule is finalized. The VA plans to reimburse eligible veterans who received care in the past year for copayment costs.
“I’m encouraged to see VA answering my call to implement the law and remove burdensome copayments for Native veterans accessing their earned health care,” said Tester in a press release. “The fact is Native veterans have bravely answered the call to duty for generations. And I’ll continue to hold VA accountable in delivering these veterans their long-overdue support.”
Surviving CLL: Higher risk of other cancer DXs
The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.
“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.
Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”
Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.
It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”
With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”
Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).
“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”
Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”
She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”
Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”
Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”
Study funding was not reported. The authors and Dr. Bond report no disclosures.
The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.
“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.
Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”
Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.
It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”
With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”
Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).
“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”
Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”
She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”
Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”
Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”
Study funding was not reported. The authors and Dr. Bond report no disclosures.
The report, which appeared in January in Blood Cancer Journal, found that patients diagnosed with CLL between 1989 and 2019 were 63% more likely to were diagnosed with SPM than a matched population: standardized incidence ratio = 1.63, 95% confidence interval (CI), 1.59-1.68.
“Our results provide patients and their treating physicians with an overview of the risk of SPM development. This information can be used in treatment decision-making and for planning appropriate surveillance activities and interventions,” study lead author Lina van der Straten, MD, PhD, of the Albert Schweitzer Hospital and Erasmus University Medical Center in the Netherlands, said in an interview.
Ohio State University hematologist David Bond, MD, who’s familiar with the findings, said in an interview that “it’s been well-established that patients with CLL are at increased risk for second primary malignancies. This is thought to be due to impaired immune surveillance and possibly carcinogenic effects of CLL treatments.” It’s not clear, he said, “whether the rate of second cancers differs between chemoimmunotherapy-treated patients and those receiving newer oral kinase inhibitors.”
Previous research into CLL and SPM has been sparse, Dr. van der Straten said, and most studies haven’t looked at SPM over time and taken into account the widespread use of chemoimmunotherapy and agents such as ibrutinib and venetoclax.
It’s important to study this topic, she said, since “cancers diagnosed after the CLL diagnosis can outweigh the improved longevity and contribute to excess morbidity and mortality in long-term CLL survivors.”
With the help of the Netherlands Cancer Registry, researchers tracked 24,815 patients with CLL who were diagnosed over the 20-year period; 4,369 developed SPM. “We demonstrated that the risk of SPM development was higher than in the general population with an excess of 125 malignancies per 10,000 person-years in the CLL cohort,” Dr. van der Straten said. “The risk of SPM development was found to be heightened in solid and hematological cancers. Patients with CLL had an increased risk of developing cancers at the following sites or types: skin, acute myeloid leukemia, soft-tissue sarcomas, thyroid, kidney, unknown primary localization, non-Hodgkin lymphomas, lung and bronchus, and colon and rectum.”
Specifically, the study reports that “elevated risk was observed for solid (SIR = 1.67; 95% CI, 1.65-1.75) and hematological SPMs (SIR = 1.42; 95% CI, 1.24-1.62). The highest risk for SPMs was noted beyond 5 years post diagnosis (SIR = 1.70; 95% CI, 1.62-1.77), for male individuals (SIR = 1.70; 95% CI, 1.64-1.77), and patients aged 18-69 years (SR = 1.92; 95% CI, 1.79-2.05).
“Patients with CLL exposed to treatment have a higher risk of SPM development than patients who will never receive therapy,” Dr. van der Straten said. Research has shown that “treatment with fludarabine, cyclophosphamide, and rituximab has been associated with a 2.38 increased risk for SPM development, particularly acute myeloid leukemia. Indeed, we found an increased risk for hematological malignancies in patients diagnosed between 2003-2009 and 2010-2019, which might be explained by the broader administration of fludarabine-based strategies in these calendar periods.”
Multiple factors could explain the higher risk of SPM in patients with CLL, including “a dysregulated immune system, treatment-related effects, and surveillance bias,” Dr. van der Straten said. “In addition, it is proposed that the immune dysfunctional nature of CLL might enhance the effect of common carcinogens, such as UV exposure and smoking, in increasing the probability of skin and respiratory cancers.”
She added that “the risk and the spectrum of SPMs were comparable for the 2003-2009 and 2010-2019 periods, suggesting that both the introduction of chemoimmunotherapy and, in part, targeted therapies did not dramatically alter the SPM landscape. However, due to the short follow-up period for the small cohort of patients receiving targeted therapies, further research is warranted.”
Dr. Bond said the findings “are largely in line with prior studies and strengthen their conclusions. Immune surveillance appears to be critical to reducing the risk for some but not all malignancies including lung cancer and melanoma, and the treatments given for CLL can cause immune suppression and thus may increase the risk.”
Moving forward, he said, “this research highlights the importance of second cancers to patients with CLL. It also highlights the need for secondary cancer screening for CLL patients, patient education to avoid known cancer risk factors including smoking and excess UV light exposure, and the need as a field to continue to invest in research into characteristics of second cancers and mitigation strategies.”
Study funding was not reported. The authors and Dr. Bond report no disclosures.
FROM BLOOD CANCER JOURNAL
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